Sertraline

From Wikipedia, the free encyclopedia

Sertraline

Clinical data
Pronunciation	/ˈsɜːrtrəˌliːn/
Trade names	Zoloft, Lustral, others
AHFS/Drugs.com	Monograph
MedlinePlus	a697048
License data	US DailyMed: Sertraline
Pregnancy category	AU: C
Addiction liability	None
Routes of administration	By mouth
Drug class	Selective serotonin reuptake inhibitor (Officially SSRI) With Weak DAT Inhibition
ATC code	N06AB06 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: ℞-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	44%
Protein binding	98.5%
Metabolism	Liver (N-demethylation mainly by CYP2B6)
Metabolites	norsertraline
Elimination half-life	~23–26 h (66 h [less-active metabolite, norsertraline])
Excretion	Kidney
Identifiers

IUPAC name
CAS Number	79617-96-2
PubChem CID	68617
IUPHAR/BPS	4798
DrugBank	DB01104
ChemSpider	61881
UNII	QUC7NX6WMB
KEGG	D02360  as HCl: D00825
ChEBI	CHEBI:9123
ChEMBL	ChEMBL809
CompTox Dashboard (EPA)	DTXSID6023577
Chemical and physical data
Formula	C17H17Cl2N
Molar mass	306.23 g·mol−1

Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. The efficacy of sertraline for depression is similar to that of other antidepressants, and the differences are mostly confined to side effects. Sertraline is better tolerated than the older tricyclic antidepressants, and it may work better than fluoxetine for some subtypes of depression. Sertraline is effective for panic disorder, social anxiety disorder, generalized anxiety disorder, and obsessive–compulsive disorder (OCD). However, for OCD, cognitive behavioral therapy, particularly in combination with sertraline, is a better treatment. Although approved for post-traumatic stress disorder, sertraline leads to only modest improvement in this condition. Sertraline also alleviates the symptoms of premenstrual dysphoric disorder and can be used in sub-therapeutic doses or intermittently for its treatment.

Sertraline shares the common side effects and contraindications of other SSRIs, with high rates of nausea, diarrhea, insomnia, and sexual side effects, but it appears not to lead to much weight gain, and its effects on cognitive performance are mild. Similar to other antidepressants, the use of sertraline for depression may be associated with a higher rate of suicidal thoughts and behavior in people under the age of 25. It should not be used together with MAO inhibitor medication: this combination causes serotonin syndrome. Sertraline taken during pregnancy is associated with a significant increase in congenital heart defects in newborns.

Sertraline was invented and developed by scientists at Pfizer and approved for medical use in the United States in 1991. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2016, sertraline was the most commonly prescribed psychiatric medication in the United States and in 2019, it was the twelfth most commonly prescribed medication in the United States, with over 37 million prescriptions.

Medical uses

Sertraline has been approved for major depressive disorder (MDD), obsessive–compulsive disorder (OCD), posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), panic disorder, and social anxiety disorder (SAD). Sertraline is not approved for use in children except for those with OCD.

Depression

Multiple controlled clinical trials established efficacy of sertraline for the treatment of depression. Sertraline is also an effective antidepressant in the routine clinical practice. Continued treatment with sertraline prevents both a relapse of the current depressive episode and future episodes (recurrence of depression).

In several double-blind studies, sertraline was consistently more effective than placebo for dysthymia, a more chronic variety of depression, and comparable to imipramine in that respect. Sertraline also improves the depression of dysthymic patients to a greater degree than psychotherapy.

Sertraline provides no benefit to children and adolescents with depression.

Comparison with other antidepressants

In general, sertraline efficacy is similar to that of other antidepressants. For example, a meta-analysis of 12 new-generation antidepressants showed that sertraline and escitalopram are the best in terms of efficacy and acceptability in the acute-phase treatment of adults with depression. Comparative clinical trials demonstrated that sertraline is similar in efficacy against depression to moclobemide, nefazodone, escitalopram, bupropion, citalopram, fluvoxamine, paroxetine, venlafaxine and mirtazapine. Sertraline may be more efficacious for the treatment of depression in the acute phase (first 4 weeks) than fluoxetine.

There are differences between sertraline and some other antidepressants in their efficacy in the treatment of different subtypes of depression and in their adverse effects. For severe depression, sertraline is as good as clomipramine but is better tolerated. Sertraline appears to work better in melancholic depression than fluoxetine, paroxetine, and mianserin and is similar to the tricyclic antidepressants such as amitriptyline and clomipramine. In the treatment of depression accompanied by OCD, sertraline performs significantly better than desipramine on the measures of both OCD and depression. Sertraline is equivalent to imipramine for the treatment of depression with co-morbid panic disorder, but it is better tolerated. Compared with amitriptyline, sertraline offered a greater overall improvement in quality of life of depressed patients.

Depression in elderly

Sertraline used for the treatment of depression in elderly (older than 60) patients is superior to placebo and comparable to another SSRI fluoxetine, and tricyclic antidepressants (TCAs) amitriptyline, nortriptyline and imipramine. Sertraline has much lower rates of adverse effects than these TCAs, with the exception of nausea, which occurs more frequently with sertraline. In addition, sertraline appears to be more effective than fluoxetine or nortriptyline in the older-than-70 subgroup. Accordingly, a meta-analysis of antidepressants in older adults found that sertraline, paroxetine and duloxetine were better than placebo. On the other hand, in a 2003 trial the effect size was modest, and there was no improvement in quality of life as compared to placebo. With depression in dementia, there is no benefit of sertraline treatment compared to either placebo or mirtazapine.

Obsessive–compulsive disorder

Sertraline is effective for the treatment of OCD in adults and children. It was better tolerated and, based on intention-to-treat analysis, performed better than the gold standard of OCD treatment clomipramine. Continuing sertraline treatment helps prevent relapses of OCD with long-term data supporting its use for up to 24 months. It is generally accepted that the sertraline dosages necessary for the effective treatment of OCD are higher than the usual dosage for depression. The onset of action is also slower for OCD than for depression. The treatment recommendation is to start treatment with a half of maximal recommended dose for at least two months. After that, the dose can be raised to the maximal recommended in the cases of unsatisfactory response.

Cognitive behavioral therapy alone was superior to sertraline in both adults and children; however, the best results were achieved using a combination of these treatments.

Panic disorder

Sertraline is superior to placebo for the treatment of panic disorder. The response rate was independent of the dose. In addition to decreasing the frequency of panic attacks by about 80% (vs. 45% for placebo) and decreasing general anxiety, sertraline resulted in improvement of quality of life on most parameters. The patients rated as "improved" on sertraline reported better quality of life than the ones who "improved" on placebo. The authors of the study argued that the improvement achieved with sertraline is different and of a better quality than the improvement achieved with placebo. Sertraline is equally effective for men and women, and for patients with or without agoraphobia. Previous unsuccessful treatment with benzodiazepines does not diminish its efficacy. However, the response rate was lower for the patients with more severe panic. Starting treatment simultaneously with sertraline and clonazepam, with subsequent gradual discontinuation of clonazepam, may accelerate the response.

Double-blind comparative studies found sertraline to have the same effect on panic disorder as paroxetine or imipramine. While imprecise, comparison of the results of trials of sertraline with separate trials of other anti-panic agents (clomipramine, imipramine, clonazepam, alprazolam, and fluvoxamine) indicates approximate equivalence of these medications.

Other anxiety disorders

Sertraline has been successfully used for the treatment of social anxiety disorder. All three major domains of the disorder (fear, avoidance, and physiological symptoms) respond to sertraline. Maintenance treatment, after the response is achieved, prevents the return of the symptoms. The improvement is greater among the patients with later, adult onset of the disorder. In a comparison trial, sertraline was superior to exposure therapy, but patients treated with the psychological intervention continued to improve during a year-long follow-up, while those treated with sertraline deteriorated after treatment termination. The combination of sertraline and cognitive behavioral therapy appears to be more effective in children and young people than either treatment alone.

Sertraline has not been approved for the treatment of generalized anxiety disorder; however, several guidelines recommend it as a first-line medication referring to good quality controlled clinical trials.

Premenstrual dysphoric disorder

Sertraline is effective in alleviating the symptoms of premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome. Significant improvement was observed in 50–60% of cases treated with sertraline vs. 20–30% of cases on placebo. The improvement began during the first week of treatment, and in addition to mood, irritability, and anxiety, improvement was reflected in better family functioning, social activity and general quality of life. Work functioning and physical symptoms, such as swelling, bloating and breast tenderness, were less responsive to sertraline. Taking sertraline only during the luteal phase, that is, the 12–14 days before menses, was shown to work as well as continuous treatment. Continuous treatment with sub-therapeutic doses of sertraline (25 mg vs. usual 50–100 mg) is also effective.

Other indications

Sertraline is approved for the treatment of post-traumatic stress disorder (PTSD). National Institute of Clinical Excellence recommends it for patients who prefer drug treatment to a psychological one. Other guidelines also suggest sertraline as a first-line option for pharmacological therapy. When necessary, long-term pharmacotherapy can be beneficial. There are both negative and positive clinical trial results for sertraline, which may be explained by the types of psychological traumas, symptoms, and comorbidities included in the various studies. Positive results were obtained in trials that included predominantly women (75%) with a majority (60%) having physical or sexual assault as the traumatic event. Contrary to the above suggestions, a meta-analysis of sertraline clinical trials for PTSD found it to be not significantly better than placebo. Another meta-analysis relegated sertraline to the second line, proposing trauma focused psychotherapy as a first-line intervention. The authors noted that Pfizer had declined to submit the results of a negative trial for the inclusion into the meta-analysis making the results unreliable.

Sertraline when taken daily can be useful for the treatment of premature ejaculation. A disadvantage of sertraline is that it requires continuous daily treatment to delay ejaculation significantly.

A 2019 systematic review suggested that sertraline may be a good way to control anger, irritability and hostility in depressed patients and patients with other comorbidities.

Contraindications

Sertraline is contraindicated in individuals taking monoamine oxidase inhibitors or the antipsychotic pimozide. Sertraline concentrate contains alcohol and is therefore contraindicated with disulfiram. The prescribing information recommends that treatment of the elderly and patients with liver impairment "must be approached with caution". Due to the slower elimination of sertraline in these groups, their exposure to sertraline may be as high as three times the average exposure for the same dose.

Side effects

See also: List of adverse effects of sertraline

Nausea, ejaculation failure, insomnia, diarrhea, dry mouth, somnolence, dizziness, tremor, and decreased libido are the common adverse effects associated with sertraline with the greatest difference from placebo. Those that most often resulted in interruption of the treatment are nausea, diarrhea and insomnia. The incidence of diarrhea is higher with sertraline—especially when prescribed at higher doses—in comparison with other SSRIs.

Over more than six months of sertraline therapy for depression, people showed a nonsignificant weight increase of 0.1%. Similarly, a 30-month-long treatment with sertraline for OCD resulted in a mean weight gain of 1.5% (1 kg). Although the difference did not reach statistical significance, the average weight gain was lower for fluoxetine (1%) but higher for citalopram, fluvoxamine and paroxetine (2.5%). Of the sertraline group, 4.5% gained a large amount of weight (defined as more than 7% gain). This result compares favorably with placebo, where, according to the literature, 3–6% of patients gained more than 7% of their initial weight. The large weight gain was observed only among female members of the sertraline group; the significance of this finding is unclear because of the small size of the group.

Over a two-week treatment of healthy volunteers, sertraline slightly improved verbal fluency but did not affect word learning, short-term memory, vigilance, flicker fusion time, choice reaction time, memory span, or psychomotor coordination. In spite of lower subjective rating, that is, feeling that they performed worse, no clinically relevant differences were observed in the objective cognitive performance in a group of people treated for depression with sertraline for 1.5 years as compared to healthy controls. In children and adolescents taking sertraline for six weeks for anxiety disorders, 18 out of 20 measures of memory, attention and alertness stayed unchanged. Divided attention was improved and verbal memory under interference conditions decreased marginally. Because of the large number of measures taken, it is possible that these changes were still due to chance. The unique effect of sertraline on dopaminergic neurotransmission may be related to these effects on cognition and vigilance.

Sertraline has a low level of exposure of an infant through the breast milk and is recommended as the preferred option for the antidepressant therapy of breast-feeding mothers. There is 29-42% increase in congenital heart defects among children whose mothers were prescribed sertraline during pregnancy, with sertraline use in the first trimester associated with 2.7-fold increase in septal heart defects.

Abrupt interruption of sertraline treatment may result in withdrawal or discontinuation syndrome. Dizziness, insomnia, anxiety, agitation, and irritability are its common symptoms. It typically occurs within a few days from drug discontinuation and lasts a few weeks. The withdrawal symptoms for sertraline are less severe and frequent than for paroxetine, and more frequent than for fluoxetine. In most cases symptoms are mild, short-lived, and resolve without treatment. More severe cases are often successfully treated by temporary reintroduction of the drug with a slower tapering off rate.

Sertraline and SSRI antidepressants in general may be associated with bruxism and other movement disorders. Sertraline appears to be associated with microscopic colitis, a rare condition of unknown etiology.

Sexual

Like other SSRIs, sertraline is associated with sexual side effects, including sexual arousal disorder, erectile dysfunction and difficulty achieving orgasm. While nefazodone and bupropion do not have negative effects on sexual functioning, 67% of men on sertraline experienced ejaculation difficulties versus 18% before the treatment. Sexual arousal disorder, defined as "inadequate lubrication and swelling for women and erectile difficulties for men", occurred in 12% of people on sertraline as compared with 1% of patients on placebo. The mood improvement resulting from the treatment with sertraline sometimes counteracted these side effects, so that sexual desire and overall satisfaction with sex stayed the same as before the sertraline treatment. However, under the action of placebo the desire and satisfaction slightly improved. Some people continue experiencing sexual side effects after they stop taking SSRIs.

Suicide

The FDA requires all antidepressants, including sertraline, to carry a boxed warning stating that antidepressants increase the risk of suicide in persons younger than 25 years. This warning is based on statistical analyses conducted by two independent groups of FDA experts that found a 100% increase of suicidal thoughts and behavior in children and adolescents, and a 50% increase - in the 18 – 24 age group.

Suicidal ideation and behavior in clinical trials are rare. For the above analysis, the FDA combined the results of 295 trials of 11 antidepressants for psychiatric indications in order to obtain statistically significant results. Considered separately, sertraline use in adults decreased the odds of suicidal behavior with a marginal statistical significance by 37% or 50% depending on the statistical technique used. The authors of the FDA analysis note that "given the large number of comparisons made in this review, chance is a very plausible explanation for this difference". The more complete data submitted later by the sertraline manufacturer Pfizer indicated increased suicidal behavior. Similarly, the analysis conducted by the UK MHRA found a 50% increase of odds of suicide-related events, not reaching statistical significance, in the patients on sertraline as compared to the ones on placebo.

Overdose

Acute overdosage is often manifested by emesis, lethargy, ataxia, tachycardia and seizures. Plasma, serum or blood concentrations of sertraline and norsertraline, its major active metabolite, may be measured to confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. As with most other SSRIs its toxicity in overdose is considered relatively low.

Interactions

Sertraline is a moderate inhibitor of CYP2D6 and CYP2B6 in vitro. Accordingly, in human trials it caused increased blood levels of CYP2D6 substrates such as metoprolol, dextromethorphan, desipramine, imipramine and nortriptyline, as well as the CYP3A4/CYP2D6 substrate haloperidol. This effect is dose-dependent; for example, co-administration with 50 mg of sertraline resulted in 20% greater exposure to desipramine, while 150 mg of sertraline led to a 70% increase. In a placebo-controlled study, the concomitant administration of sertraline and methadone caused a 40% increase in blood levels of the latter, which is primarily metabolized by CYP2B6.

Sertraline had a slight inhibitory effect on the metabolism of diazepam, tolbutamide and warfarin, which are CYP2C9 or CYP2C19 substrates; the clinical relevance of this effect was unclear. As expected from in vitro data, sertraline did not alter the human metabolism of the CYP3A4 substrates erythromycin, alprazolam, carbamazepine, clonazepam, and terfenadine; neither did it affect metabolism of the CYP1A2 substrate clozapine.

Sertraline had no effect on the actions of digoxin and atenolol, which are not metabolized in the liver. Case reports suggest that taking sertraline with phenytoin or zolpidem may induce sertraline metabolism and decrease its efficacy, and that taking sertraline with lamotrigine may increase the blood level of lamotrigine, possibly by inhibition of glucuronidation.

CYP2C19 inhibitor esomeprazole increased sertraline concentrations in blood plasma by approximately 40%.

Clinical reports indicate that interaction between sertraline and the MAOIs isocarboxazid and tranylcypromine may cause serotonin syndrome. In a placebo-controlled study in which sertraline was co-administered with lithium, 35% of the subjects experienced tremors, while none of those taking placebo did.

Sertraline may interact with grapefruit juice - see Grapefruit–drug interactions.

Pharmacology

Pharmacodynamics

Sertraline is a selective serotonin reuptake inhibitor (SSRI). By binding serotonin transporter (SERT) it inhibits neuronal reuptake of serotonin and potentiates serotonergic activity in the central nervous system. It does not significantly affect norepinephrine transporter (NET), serotonin, dopamine, adrenergic, histamine, acetylcholine, GABA or benzodiazepine receptors.

Sertraline also shows relatively high activity as an inhibitor of the dopamine transporter (DAT) and antagonist of the sigma σ₁ receptor (but not the σ₂ receptor). However, sertraline affinity for its main target (SERT) is much greater than its affinity for σ₁ receptor and DAT. Although there could be a role for the σ₁ receptor in the pharmacology of sertraline, the significance of this receptor in its actions is unclear. Similarly, the clinical relevance of sertraline's blockade of the dopamine transporter is uncertain.

Pharmacokinetics

Desmethylsertraline—sertraline's major metabolite

Sertraline is absorbed slowly when taken orally, achieving its maximal concentration in the plasma 4 to 6 hours after ingestion. In the blood, it is 98.5% bound to plasma proteins. Its half-life in the body is 13–45 hours and, on average, is about 1.5 times longer in women (32 hours) than in men (22 hours), leading to a 1.5-times-higher exposure in women. According to in vitro studies, sertraline is metabolized by multiple cytochrome 450 isoforms; however, it appears that in the human body CYP2C19 plays the most important role, followed by CYP2B6. Poor CYP2C19 metabolizers have 2.7-fold higher levels of sertraline, and intermediate metabolizers - 1.4-fold higher levels, than normal (extensive) metabolizers. In contrast, poor CYP2B6 metabolizers have 1.6-fold higher levels of sertraline and intermediate metabolizers - 1.2-fold higher levels.

The major metabolite of sertraline, desmethylsertraline, is about 50 times weaker as a serotonin transporter inhibitor than sertraline and its clinical effect is negligible.^[106] Sertraline can be deaminated in vitro by monoamine oxidases; however, this metabolic pathway has never been studied in vivo.

History

Skeletal formulae of thiothixene, lometraline and tametraline, from which sertraline was derived. Commonalities to the structure of sertraline are highlighted in green.

The history of sertraline dates back to the early 1970s, when Pfizer chemist Reinhard Sarges invented a novel series of psychoactive compounds, including lometraline, based on the structures of the neuroleptics thiothixene and pinoxepin. Further work on these compounds led to tametraline, a norepinephrine and weaker dopamine reuptake inhibitor. Development of tametraline was soon stopped because of undesired stimulant effects observed in animals. A few years later, in 1977, pharmacologist Kenneth Koe, after comparing the structural features of a variety of reuptake inhibitors, became interested in the tametraline series. He asked another Pfizer chemist, Willard Welch, to synthesize some previously unexplored tametraline derivatives. Welch generated a number of potent norepinephrine and triple reuptake inhibitors, but to the surprise of the scientists, one representative of the generally inactive cis-analogs was a serotonin reuptake inhibitor. Welch then prepared stereoisomers of this compound, which were tested in vivo by animal behavioral scientist Albert Weissman. The most potent and selective (+)-isomer was taken into further development and eventually named sertraline. Weissman and Koe recalled that the group did not set up to produce an antidepressant of the SSRI type—in that sense their inquiry was not "very goal driven", and the discovery of the sertraline molecule was serendipitous. According to Welch, they worked outside the mainstream at Pfizer, and even "did not have a formal project team". The group had to overcome initial bureaucratic reluctance to pursue sertraline development, as Pfizer was considering licensing an antidepressant candidate from another company.

Sertraline was approved by the US Food and Drug Administration (FDA) in 1991 based on the recommendation of the Psychopharmacological Drugs Advisory Committee; it had already become available in the United Kingdom the previous year. The FDA committee achieved a consensus that sertraline was safe and effective for the treatment of major depression. During the discussion, Paul Leber, the director of the FDA Division of Neuropharmacological Drug Products, noted that granting approval was a "tough decision", since the treatment effect on outpatients with depression had been "modest to minimal". Other experts emphasized that the drug's effect on inpatients had not differed from placebo and criticized poor design of the clinical trials by Pfizer. For example, 40% of participants dropped out of the trials, significantly decreasing their validity.

Until 2002, sertraline was only approved for use in adults ages 18 and over; that year, it was approved by the FDA for use in treating children aged 6 or older with severe OCD. In 2003, the UK Medicines and Healthcare products Regulatory Agency issued a guidance that, apart from fluoxetine (Prozac), SSRIs are not suitable for the treatment of depression in patients under 18. However, sertraline can still be used in the UK for the treatment of OCD in children and adolescents. In 2005, the FDA added a boxed warning concerning pediatric suicidal behavior to all antidepressants, including sertraline. In 2007, labeling was again changed to add a warning regarding suicidal behavior in young adults ages 18 to 24.

Society and culture

Generic availability

The US patent for Zoloft expired in 2006, and sertraline is available in generic form and is marketed under many brand names worldwide.

In May 2020, the FDA placed Zoloft on the list of drugs currently facing a shortage.

 

Sensory processing sensitivity

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Sensory_processing_sensitivity 

Characteristics of SPS as graphically summarized by Greven et al. (review article, 2019) A person with a high measure of SPS is said to be a highly sensitive person (HSP).

Sensory processing sensitivity (SPS) is a temperamental or personality trait involving "an increased sensitivity of the central nervous system and a deeper cognitive processing of physical, social and emotional stimuli". The trait is characterized by "a tendency to 'pause to check' in novel situations, greater sensitivity to subtle stimuli, and the engagement of deeper cognitive processing strategies for employing coping actions, all of which is driven by heightened emotional reactivity, both positive and negative".

A human with a particularly high measure of SPS is considered to have "hypersensitivity", or be a highly sensitive person (HSP). The terms SPS and HSP were coined in the mid-1990s by psychologists Elaine Aron and her husband Arthur Aron, who developed the Highly Sensitive Person Scale (HSPS) questionnaire by which SPS is measured. Other researchers have applied various other terms to denote this responsiveness to stimuli that is seen in humans and other species.

According to the Arons and colleagues, people with high SPS make up about 15–20% of the population. Although some researchers consistently related high SPS to negative outcomes, other researchers have associated it with increased responsiveness to both positive and negative influences. Aron and colleagues state that the high-SPS personality trait is not a disorder.

Origin and development of the terms

Elaine Aron's book The Highly Sensitive Person was published in 1996. In 1997 Elaine and Arthur Aron formally identified sensory processing sensitivity (SPS) as the defining trait of highly sensitive persons (HSPs). The popular terms hypersensitivity (not to be confused with the medical term hypersensitivity) or highly sensitive are popular synonyms for the scientific concept of SPS. By way of definition, Aron and Aron (1997) wrote that sensory processing here refers not to the sense organs themselves, but to what occurs as sensory information is transmitted to or processed in the brain. They assert that the trait is not a disorder but an innate survival strategy that has both advantages and disadvantages.

Elaine Aron's academic journal articles as well as self-help publications for the lay reader have focused on distinguishing high SPS from socially reticent behavior and disorders with which high SPS can be confused; overcoming the social unacceptability that can cause low self-esteem; and emphasizing the advantages of high SPS to balance the disadvantages emphasized by others.

In 2015, sociologist Elizabeth Bernstein wrote in The Wall Street Journal that HSPs were "having a moment," noting that several hundred research studies had been conducted on topics related to HSPs' high sensitivity. The First International Scientific Conference on High Sensitivity or Sensory Processing Sensitivity was held at the Vrije Universiteit Brussel. By 2015, more than a million copies of The Highly Sensitive Person had been sold.

Earlier research

Research pre-dating the Arons' coining of the term "high sensitivity" includes that of German medicine professor Wolfgang Klages, who argued in the 1970s that the phenomenon of sensitive and highly sensitive humans is "biologically anchored" and that the "stimulus threshold of the thalamus" is much lower in these persons. As a result, said Klages, there is a higher permeability for incoming signals from afferent nerve fibers so that they pass "unfiltered" to the cerebral cortex.

The Arons (1997) recognized psychologist Albert Mehrabian's (1976, 1980, 1991) concept of filtering the "irrelevant", but wrote that the concept implied that the inability of HSPs' (Mehrabian's "low screeners") to filter out what is irrelevant would imply that what is relevant is determined from the perspective of non-HSPs ("high screeners").

Attributes, characteristics and prevalence

Boterberg et al. (2016) describe high SPS as a "temperamental or personality trait which is present in some individuals and reflects an increased sensitivity of the central nervous system and a deeper cognitive processing of physical, social and emotional stimuli".

People with high SPS report having a heightened response to stimuli such as pain, caffeine, hunger, and loud noises. According to Boterberg et al., these individuals are "believed to be easily overstimulated by external stimuli because they have a lower perceptual threshold and process stimuli cognitively deeper than most other people." This deeper processing may result in increased reaction time as more time is spent responding to cues in the environment, and might also contribute to cautious behavior and low risk-taking.

SPS involves responsiveness to both environmental adversity and positive environmental aspects, respectively modeled by the diathesis-stress model and the vantage sensitivity framework.

The HSP Scale, initially (1997) a questionnaire designed to measure SPS on a unidimensional scale, was subsequently decomposed into two, three, or four factors or sub-scales. Most components have been associated with traditionally accepted negative psychological outcomes including high stress levels, being easily overwhelmed, increased rates of depression, anxiety, and sleep problems, as well as symptoms of autism; the diathesis-stress model focused on increased vulnerability to negative influences. However, the differential susceptibility theory (DST) and biological sensitivity to context theory (BSCT) and sensory processing sensitivity (SPS) suggest increased plasticity in terms of responsiveness to both positive and negative influences; and the vantage sensitivity (VS) concept emphasizes increased responsiveness to positive experiences. Researchers such as Smolewska et al. (2006) said positive outcomes were more common in individuals with high aesthetic sensitivity, who tend to experience heightened positive emotions in response to rewarding stimuli and more likely to score high on "openness" on the Big Five factors model.

Research in evolutionary biology provides evidence that the trait of SPS can be observed, under various terms, in over 100 nonhuman species, Aron writing that the SPS trait is meant to encompass what personality psychologists have described under various other names. Conversely, Aron has distinguished SPS from what she considers it is not, explicitly distinguishing high SPS from possibly similar-appearing traits or disorders (such as shyness, sensation-seeking, sensory processing disorder, and autism), and further, that SPS may be a basic variable that may underlie multiple other trait differences (such as introversion versus extraversion). Contrary to common misconception, according to Aron HSPs include both introverts and extroverts, and may be simultaneously high-sensation seeking and cautious.

In humans and other species, responsive and unresponsive individuals coexist and consistently display different levels of responsiveness to environmental stimuli, the different levels of responsiveness having corresponding evolutionary costs and benefits. This observation parallels Aron's assertion that high SPS is not a disorder, but rather a personality trait with attendant advantages and disadvantages. Accordingly, Aron cautions medical professionals against prescribing psychoactive medications to "cure" the trait, which may or may not coexist with an actual disorder.

By 2015 the trait had been documented at various levels of study, including temperament and behavior psychology, brain function and neuronal sensitization, and genetics. For example, genetic studies provide evidence that higher levels of SPS are linked to the serotonin transporter 5-HTTLPR short/short genotype, polymorphisms in dopamine neurotransmitter genes, and the ADRA2b norepinephrine-related gene variant.

HSP Scale score patterns in adults were thought to be distributed as a dichotomous categorical variable with a break point between 10% and 35%, with Aron choosing a cut-off of the highest-scoring 20% of individuals to define the HSP category. A 2019 review article stated that findings suggest people fall into three sensitivity groups along a normal distribution sensitivity continuum.

 

Social anxiety disorder

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Social_anxiety_disorder 

Social anxiety disorder
Other names	Social phobia
Specialty	Psychiatry
Symptoms	Social isolation, hypervigilance, feeling of inferiority, low self-esteem, difficulty socializing with others
Usual onset	Usually during teen years
Risk factors	Genetic factors, preexisting mental disorder
Treatment	Psychotherapy, antidepressant medication, benzodiazapines, pregabalin
Frequency	7.1% per year

Social anxiety disorder (SAD), also known as social phobia, is an anxiety disorder characterized by sentiments of fear and anxiety in social situations, causing considerable distress and impaired ability to function in at least some aspects of daily life. These fears can be triggered by perceived or actual scrutiny from others. Individuals with social anxiety disorder fear negative evaluations from other people.

Physical symptoms often include excessive blushing, excess sweating, trembling, palpitations, and nausea. Stammering may be present, along with rapid speech. Panic attacks can also occur under intense fear and discomfort. Some sufferers may use alcohol or other drugs to reduce fears and inhibitions at social events. It is common for sufferers of social phobia to self-medicate in this fashion, especially if they are undiagnosed, untreated, or both; this can lead to alcohol use disorder, eating disorders or other kinds of substance use disorders. SAD is sometimes referred to as an illness of lost opportunities where "individuals make major life choices to accommodate their illness". According to ICD-10 guidelines, the main diagnostic criteria of social phobia are fear of being the focus of attention, or fear of behaving in a way that will be embarrassing or humiliating, avoidance and anxiety symptoms. Standardized rating scales can be used to screen for social anxiety disorder and measure the severity of anxiety.

The first line of treatment for social anxiety disorder is cognitive behavioral therapy (CBT). Medications such as SSRIs are effective for social phobia, especially paroxetine. CBT is effective in treating this disorder, whether delivered individually or in a group setting. The cognitive and behavioral components seek to change thought patterns and physical reactions to anxiety-inducing situations. The attention given to social anxiety disorder has significantly increased since 1999 with the approval and marketing of drugs for its treatment. Prescribed medications include several classes of antidepressants: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors (MAOIs). Other commonly used medications include beta blockers and benzodiazepines.

History

Literary descriptions of shyness can be traced back to the days of Hippocrates around 400 B.C. Hippocrates described someone who "through bashfulness, suspicion, and timorousness, will not be seen abroad; loves darkness as life and cannot endure the light or to sit in lightsome places; his hat still in his eyes, he will neither see, nor be seen by his good will. He dare not come in company for fear he should be misused, disgraced, overshoot himself in gesture or speeches, or be sick; he thinks every man observes him."

The first mention of the psychiatric term "social phobia" (phobie des situations sociales) was made in the early 1900s. Psychologists used the term "social neurosis" to describe extremely shy patients in the 1930s. After extensive work by Joseph Wolpe on systematic desensitization, research on phobias and their treatment grew. The idea that social phobia was a separate entity from other phobias came from the British psychiatrist Isaac Marks in the 1960s. This was accepted by the American Psychiatric Association and was first officially included in the third edition of the Diagnostic and Statistical Manual of Mental Disorders. The definition of the phobia was revised in 1989 to allow comorbidity with avoidant personality disorder and introduced generalized social phobia. Social phobia had been largely ignored prior to 1985.

After a call to action by psychiatrist Michael Liebowitz and clinical psychologist Richard Heimberg, there was an increase in attention to and research on the disorder. The DSM-IV gave social phobia the alternative name "social anxiety disorder". Research on the psychology and sociology of everyday social anxiety continued. Cognitive Behavioural models and therapies were developed for social anxiety disorder. In the 1990s, paroxetine became the first prescription drug in the U.S. approved to treat social anxiety disorder, with others following.

Signs and symptoms

The 10th version of the International Classification of Diseases (ICD-10) classifies social anxiety as a mental and behavioral disorder.

Cognitive aspects

In cognitive models of social anxiety disorder, those with social phobias experience dread over how they will present to others. They may feel overly self-conscious, pay high self-attention after the activity, or have high performance standards for themselves. According to the social psychology theory of self-presentation, a sufferer attempts to create a well-mannered impression towards others but believes they are unable to do so. Many times, before the potentially anxiety-provoking social situation, sufferers may deliberately review what could go wrong and how to deal with each unexpected case. After the event, they may have the perception that they performed unsatisfactorily. Consequently, they will perceive anything that may have possibly been abnormal as embarrassing. These thoughts may extend for weeks or longer. Cognitive distortions are a hallmark and are learned about in CBT (cognitive-behavioral therapy). Thoughts are often self-defeating and inaccurate. Those with social phobia tend to interpret neutral or ambiguous conversations with a negative outlook and many studies suggest that socially anxious individuals remember more negative memories than those less distressed.

An example of an instance may be that of an employee presenting to their co-workers. During the presentation, the person may stutter a word, upon which they may worry that other people significantly noticed and think that their perceptions of them as a presenter have been tarnished. This cognitive thought propels further anxiety which compounds further stuttering, sweating, and, potentially, a panic attack.

Behavioural aspects

Social anxiety disorder is a persistent fear of one or more situations in which the person is exposed to possible scrutiny by others and fears that they may do something or act in a way that will be humiliating or embarrassing. It exceeds normal "shyness" as it leads to excessive social avoidance and substantial social or occupational impairment. Feared activities may include almost any type of social interaction, especially small groups, dating, parties, talking to strangers, restaurants, interviews, etc.

Those who have social anxiety disorder fear being judged by others in society. In particular, individuals with social anxiety are nervous in the presence of people with authority and feel uncomfortable during physical examinations. People who have this disorder may behave a certain way or say something and then feel embarrassed or humiliated after. As a result, they often choose to isolate themselves from society to avoid such situations. They may also feel uncomfortable meeting people they do not know and act distant when they are with large groups of people. In some cases, they may show evidence of this disorder by avoiding eye contact, or blushing when someone is talking to them.

According to psychologist B. F. Skinner, phobias are controlled by escape and avoidance behaviors. For instance, a student may leave the room when talking in front of the class (escape) and refrain from doing verbal presentations because of the previously encountered anxiety attack (avoid). Major avoidance behaviors could include an almost pathological or compulsive lying behavior to preserve self-image and avoid judgment in front of others. Minor avoidance behaviors are exposed when a person avoids eye contact and crosses his/her arms to conceal recognizable shaking. A fight-or-flight response is then triggered in such events.

Physiological aspects

Physiological effects, similar to those in other anxiety disorders, are present in social phobias. In adults, it may be tears as well as excessive sweating, nausea, difficulty breathing, shaking, and palpitations as a result of the fight-or-flight response. The walk disturbance (where a person is so worried about how they walk that they may lose balance) may appear, especially when passing a group of people. Blushing is commonly exhibited by individuals suffering from social phobia. These visible symptoms further reinforce the anxiety in the presence of others. A 2006 study found that the area of the brain called the amygdala, part of the limbic system, is hyperactive when patients are shown threatening faces or confronted with frightening situations. They found that patients with more severe social phobia showed a correlation with the increased response in the amygdala.

Social aspects

People with SAD avoid situations that most people consider "normal". They may have a hard time understanding how others can handle these situations so easily. People with SAD avoid all or most social situations and hide from others, which can affect their personal relationships. Social phobia can completely remove people from social situations due to the irrational fear of these situations. People with SAD may be addicted to social media networks, have sleep deprivation, and feel good when they avoid human interactions. SAD can also lead to low self-esteem, negative thoughts, major depressive disorder, sensitivity to criticism, and poor social skills that don't improve. People with SAD experience anxiety in a variety of social situations, from important, meaningful encounters, to everyday trivial ones. These people may feel more nervous in job interviews, dates, interactions with authority, or at work.

Comorbidity

SAD shows a high degree of co-occurrence with other psychiatric disorders. In fact, a population-based study found that 66% of those with SAD had one or more additional mental health disorders. SAD often occurs alongside low self-esteem and most commonly clinical depression, perhaps due to a lack of personal relationships and long periods of isolation related to social avoidance. Clinical depression is 1.49 to 3.5 times more likely to occur in those with SAD. Research also indicates that the presence of certain social fears (e.g., avoidance of participating in small groups, avoidance of going to a party) are more likely to trigger comorbid depressive symptoms than other social fears, and thus deserve a very careful audit during clinical assessment among patients with SAD.

Anxiety disorders other than SAD are also very common in patients with SAD, in particular generalized anxiety disorder. Avoidant personality disorder is likewise highly correlated with SAD, with comorbidity rates ranging from 25% to 89%.

To try to reduce their anxiety and alleviate depression, people with social phobia may use alcohol or other drugs, which can lead to substance use disorders. It is estimated that one-fifth of patients with social anxiety disorder also have alcohol use disorder. However, some research suggests SAD is unrelated to, or even protective against alcohol-related problems. Those who have both alcohol use disorder and social anxiety disorder are more likely to avoid group-based treatments and to relapse compared to people who do not have this combination.

Causes

Research into the causes of social anxiety and social phobia is wide-ranging, encompassing multiple perspectives from neuroscience to sociology. Scientists have yet to pinpoint the exact causes. Studies suggest that genetics can play a part in combination with environmental factors. Social phobia is not caused by other mental disorders or substance use. Generally, social anxiety begins at a specific point in an individual's life. This will develop over time as the person struggles to recover. Eventually, mild social awkwardness can develop into symptoms of social anxiety or phobia. Passive social media usage may cause social anxiety in some people.

Genetics

It has been shown that there is a two to a threefold greater risk of having social phobia if a first-degree relative also has the disorder. This could be due to genetics and/or due to children acquiring social fears and avoidance through processes of observational learning or parental psychosocial education. Studies of identical twins brought up (via adoption) in different families have indicated that, if one twin developed social anxiety disorder, then the other was between 30 percent and 50 percent more likely than average to also develop the disorder. To some extent, this "heritability" may not be specific – for example, studies have found that if a parent has any kind of anxiety disorder or clinical depression, then a child is somewhat more likely to develop an anxiety disorder or social phobia. Studies suggest that parents of those with social anxiety disorder tend to be more socially isolated themselves (Bruch and Heimberg, 1994; Caster et al., 1999), and shyness in adoptive parents is significantly correlated with shyness in adopted children (Daniels and Plomin, 1985).

Growing up with overprotective and hypercritical parents has also been associated with social anxiety disorder. Adolescents who were rated as having an insecure (anxious-ambivalent) attachment with their mother as infants were twice as likely to develop anxiety disorders by late adolescence, including social phobia.

A related line of research has investigated 'behavioural inhibition' in infants – early signs of an inhibited and introspective or fearful nature. Studies have shown that around 10–15 percent of individuals show this early temperament, which appears to be partly due to genetics. Some continue to show this trait into adolescence and adulthood and appear to be more likely to develop a social anxiety disorder.

Social experiences

A previous negative social experience can be a trigger to social phobia, perhaps particularly for individuals high in "interpersonal sensitivity". For around half of those diagnosed with social anxiety disorder, a specific traumatic or humiliating social event appears to be associated with the onset or worsening of the disorder; this kind of event appears to be particularly related to specific social phobia, for example, regarding public speaking (Stemberg et al., 1995). As well as direct experiences, observing or hearing about the socially negative experiences of others (e.g. a faux pas committed by someone), or verbal warnings of social problems and dangers, may also make the development of a social anxiety disorder more likely. Social anxiety disorder may be caused by the longer-term effects of not fitting in, or being bullied, rejected, or ignored (Beidel and Turner, 1998). Shy adolescents or avoidant adults have emphasized unpleasant experiences with peers or childhood bullying or harassment (Gilmartin, 1987). In one study, popularity was found to be negatively correlated with social anxiety, and children who were neglected by their peers reported higher social anxiety and fear of negative evaluation than other categories of children. Socially phobic children appear less likely to receive positive reactions from peers, and anxious or inhibited children may isolate themselves.

Cultural influences

Cultural factors that have been related to social anxiety disorder include a society's attitude towards shyness and avoidance, affecting the ability to form relationships or access employment or education, and shame. One study found that the effects of parenting are different depending on the culture: American children appear more likely to develop social anxiety disorder if their parents emphasize the importance of others' opinions and use shame as a disciplinary strategy (Leung et al., 1994), but this association was not found for Chinese/Chinese-American children. In China, research has indicated that shy-inhibited children are more accepted than their peers and more likely to be considered for leadership and considered competent, in contrast to the findings in Western countries. Purely demographic variables may also play a role.

Problems in developing social skills, or 'social fluency', may be a cause of some social anxiety disorder, through either inability or lack of confidence to interact socially and gain positive reactions and acceptance from others. The studies have been mixed, however, with some studies not finding significant problems in social skills while others have. What does seem clear is that the socially anxious perceive their own social skills to be low. It may be that the increasing need for sophisticated social skills in forming relationships or careers, and an emphasis on assertiveness and competitiveness, is making social anxiety problems more common, at least among the 'middle classes'. An interpersonal or media emphasis on 'normal' or 'attractive' personal characteristics has also been argued to fuel perfectionism and feelings of inferiority or insecurity regarding negative evaluation from others. The need for social acceptance or social standing has been elaborated in other lines of research relating to social anxiety.

Substance-induced

While alcohol initially relieves social phobia, excessive alcohol misuse can worsen social phobia symptoms and cause panic disorder to develop or worsen during alcohol intoxication and especially during alcohol withdrawal syndrome. This effect is not unique to alcohol but can also occur with long-term use of drugs that have a similar mechanism of action to alcohol such as the benzodiazepines which are sometimes prescribed as tranquillisers. Benzodiazepines possess anti-anxiety properties and can be useful for the short-term treatment of severe anxiety. Like the anticonvulsants, they tend to be mild and well-tolerated, although there is a risk of habit-forming. Benzodiazepines are usually administered orally for the treatment of anxiety; however, occasionally lorazepam or diazepam may be given intravenously for the treatment of panic attacks.

The World Council of Anxiety does not recommend benzodiazepines for the long-term treatment of anxiety due to a range of problems associated with long-term use including tolerance, psychomotor impairment, cognitive and memory impairments, physical dependence and a benzodiazepine withdrawal syndrome upon discontinuation of benzodiazepines. Despite increasing focus on the use of antidepressants and other agents for the treatment of anxiety, benzodiazepines have remained a mainstay of anxiolytic pharmacotherapy due to their robust efficacy, rapid onset of therapeutic effect, and generally favorable side effect profile. Treatment patterns for psychotropic drugs appear to have remained stable over the past decade, with benzodiazepines being the most commonly used medication for panic disorder.

Many people who are addicted to alcohol or prescribed benzodiazepines when it is explained to them they have a choice between ongoing ill mental health or quitting and recovering from their symptoms decide on quitting alcohol or their benzodiazepines. Symptoms may temporarily worsen however, during alcohol withdrawal or benzodiazepine withdrawal.

Psychological factors

Research has indicated the role of 'core' or 'unconditional' negative beliefs (e.g. "I am inept") and 'conditional' beliefs nearer to the surface (e.g. "If I show myself, I will be rejected"). They are thought to develop based on personality and adverse experiences and to be activated when the person feels under threat. Recent research has also highlighted that conditional beliefs may also be at play (e.g., "If people see I'm anxious, they'll think that I'm weak").

A secondary factor is self-concealment which involves concealing the expression of one's anxiety or its underlying beliefs. One line of work has focused more specifically on the key role of self-presentational concerns. The resulting anxiety states are seen as interfering with social performance and the ability to concentrate on interaction, which in turn creates more social problems, which strengthens the negative schema. Also highlighted has been a high focus on and worry about anxiety symptoms themselves and how they might appear to others. A similar model emphasizes the development of a distorted mental representation of the self and overestimates of the likelihood and consequences of negative evaluation, and of the performance standards that others have. Such cognitive-behavioral models consider the role of negatively biased memories of the past and the processes of rumination after an event, and fearful anticipation before it.

Studies have also highlighted the role of subtle avoidance and defensive factors, and shown how attempts to avoid feared negative evaluations or use of 'safety behaviors' (Clark & Wells, 1995) can make social interaction more difficult and the anxiety worse in the long run. This work has been influential in the development of Cognitive Behavioral Therapy for social anxiety disorder, which has been shown to have efficacy.

Mechanisms

There are many studies investigating neural bases of social anxiety disorder. Although the exact neural mechanisms have not been found yet, there is evidence relating social anxiety disorder to imbalance in some neurochemicals and hyperactivity in some brain areas.

Neurotransmitters

Sociability is closely tied to dopaminergic neurotransmission. In a 2011 study, a direct relation between social status of volunteers and binding affinity of dopamine D2/3 receptors in the striatum was found. Other research shows that the binding affinity of dopamine D2 receptors in the striatum of social anxiety sufferers is lower than in controls. Some other research shows an abnormality in dopamine transporter density in the striatum of social anxiety sufferers. However, some researchers have been unable to replicate previous findings of evidence of dopamine abnormality in social anxiety disorder. Studies have shown high prevalence of social anxiety in Parkinson's disease and schizophrenia. In a recent study, social phobia was diagnosed in 50% of Parkinson's disease patients. Other researchers have found social phobia symptoms in patients treated with dopamine antagonists like haloperidol, emphasizing the role of dopamine neurotransmission in social anxiety disorder.

Some evidence points to the possibility that social anxiety disorder involves reduced serotonin receptor binding. A recent study reports increased serotonin transporter binding in psychotropic medication-naive patients with generalized social anxiety disorder. Although there is little evidence of abnormality in serotonin neurotransmission, the limited efficacy of medications which affect serotonin levels may indicate the role of this pathway. Paroxetine, sertraline and fluvoxamine are three SSRIs that have been approved by the FDA to treat social anxiety disorder. Some researchers believe that SSRIs decrease the activity of the amygdala. There is also increasing focus on other candidate transmitters, e.g. norepinephrine and glutamate, which may be over-active in social anxiety disorder, and the inhibitory transmitter GABA, which may be under-active in the thalamus.

Brain areas

The amygdala is part of the limbic system which is related to fear cognition and emotional learning. Individuals with social anxiety disorder have been found to have a hypersensitive amygdala; for example in relation to social threat cues (e.g. perceived negative evaluation by another person), angry or hostile faces, and while waiting to give a speech. Recent research has also indicated that another area of the brain, the anterior cingulate cortex, which was already known to be involved in the experience of physical pain, also appears to be involved in the experience of 'social pain', for example perceiving group exclusion. Recent research also highlighted the potent role of the prefrontal cortex, especially its dorsolateral part, in the maintenance of cognitive biases involved in SAD. A 2007 meta-analysis also found that individuals with social anxiety had hyperactivation in the amygdala and insula areas which are frequently associated with fear and negative emotional processing.

Diagnosis

ICD-10 defines social phobia as fear of scrutiny by other people leading to avoidance of social situations. The anxiety symptoms may present as a complaint of blushing, hand tremor, nausea, or urgency of micturition. Symptoms may progress to panic attacks.

Standardized rating scales such as the Social Phobia Inventory, the SPAI-B, Liebowitz Social Anxiety Scale, and the Social Interaction Anxiety Scale can be used to screen for social anxiety disorder and measure the severity of anxiety.

DSM-V Diagnosis

DSM-5 defines Social Anxiety Disorder as a marked, or intense, fear or anxiety of social situations in which the individual may be scrutinized by others.

DSM-5 Diagnostic Criteria with Diagnostic Features:

1. Marked fear or anxiety about one or more social situations in which the individual is exposed to possible scrutiny by others. Examples include social interactions (e.g., having a conversation, meeting unfamiliar people), being observed (e.g., eating or drinking), and performing in front of others (e.g., giving a speech). Note: In children, the anxiety must occur in peer settings and not just during interactions with adults.
2. The individual fears that he or she will act in a way or show anxiety symptoms that will be negatively evaluated (i.e., will be humiliating or embarrassing: will lead to rejection or offend others). When exposed to such social situations, the individual fears that he or she will be negatively evaluated. The individual is concerned that he or she will be judged as anxious, weak, crazy, stupid, boring, intimidating, dirty, or unlikable. The individual fears that he or she will act or appear in a certain way or show anxiety symptoms, such as blushing, trembling, sweating, stumbling over one's words, or staring, that will be negatively evaluated by others.
3. The social situations almost always provoke fear or anxiety. Thus, an individual who becomes anxious only occasionally in the social situation(s) would not be diagnosed with social anxiety disorder. Note: In children, the fear or anxiety may be expressed by crying, tantrums, freezing, clinging, shrinking, or failing to speak in social situations.
4. The social situations are avoided or endured with intense fear or anxiety. Alternatively, the situations are endured with intense fear or anxiety.
5. The fear or anxiety is out of proportion to the actual threat posed by the social situation and to the sociocultural context. The fear or anxiety is judged to be out of proportion to the actual risk of being negatively evaluated or to the consequences of such negative evaluation. Sometimes, the anxiety may not be judged to be excessive, because it is related to an actual danger (e.g., being bullied or tormented by others). However, individuals with social anxiety disorder often overestimate the negative consequences of social situations, and thus the judgment of being out of proportion is made by the clinician.
6. The fear, anxiety, or avoidance is persistent, typically lasting for 6 months or more. This duration threshold helps distinguish the disorder from transient social fears that are common, particularly among children and in the community. However, the duration criterion should be used as a general guide, with allowance for some degree of flexibility.
7. The fear, anxiety, or avoidance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. The fear, anxiety, and avoidance must interfere significantly with the individual's normal routine, occupational or academic functioning, or social activities or relationships, or must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. For example, an individual who is afraid to speak in public would not receive a diagnosis of social anxiety disorder if this activity is not routinely encountered on the job or in classroom work, and if the individual is not significantly distressed about it. However, if the individual avoids, or is passed over for, the job or education he or she really wants because of social anxiety symptoms criterion is met.
8. The fear, anxiety, or avoidance is not attributable to the physiological effects of a substance (e.g., an addictive substance, a medication) or another medical condition.
9. The fear, anxiety, or avoidance is not better explained by the symptoms of another mental disorder, such as panic disorder, body dysmorphic disorder, or autism spectrum disorder.
10. If another medical condition (e.g., Parkinson disease, obesity, disfigurement from burns or injury) is present, the fear, anxiety, or avoidance is clearly unrelated or is excessive.

If the fear is restricted to speaking or performing in public it is performance only social anxiety disorder.

Differential diagnosis

The DSM-IV criteria stated that an individual cannot receive a diagnosis of social anxiety disorder if their symptoms are better accounted for by one of the autism spectrum disorders such as autism and Asperger syndrome.

Because of its close relationship and overlapping symptoms, treating people with social phobia may help understand the underlying connections to other mental disorders. Social anxiety disorder is often linked to bipolar disorder and attention deficit hyperactivity disorder (ADHD) and some believe that they share an underlying cyclothymic-anxious-sensitive disposition. The co-occurrence of ADHD and social phobia is very high, especially when SCT symptoms are present.

Prevention

Prevention of anxiety disorders is one focus of research. Use of CBT and related techniques may decrease the number of children with social anxiety disorder following completion of prevention programs.

Treatment

Psychotherapies

The first-line treatment for social anxiety disorder is cognitive behavioral therapy (CBT) with medications such as selective serotonin reuptake inhibitors (SSRIs) used only in those who are not interested in therapy. Self-help based on principles of CBT is a second-line treatment.

There is some emerging evidence for the use of acceptance and commitment therapy (ACT) in the treatment of social anxiety disorder. ACT is considered an offshoot of traditional CBT and emphasizes accepting unpleasant symptoms rather than fighting against them, as well as psychological flexibility – the ability to adapt to changing situational demands, to shift one's perspective, and to balance competing desires. ACT may be useful as a second line treatment for this disorder in situations where CBT is ineffective or refused.

Some studies have suggested social skills training (SST) can help with social anxiety.  Examples of social skills focused on during SST for social anxiety disorder include: initiating conversations, establishing friendships, interacting with members of the preferred sex, constructing a speech and assertiveness skills. However, it is not clear whether specific social skills techniques and training are required, rather than just support with general social functioning and exposure to social situations.

Given the evidence that social anxiety disorder may predict subsequent development of other psychiatric disorders such as depression, early diagnosis and treatment is important. Social anxiety disorder remains under-recognized in primary care practice, with patients often presenting for treatment only after the onset of complications such as clinical depression or substance use disorders.

Medications

SSRIs

Selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants, are the first choice of medication for generalized social phobia but a second-line treatment. Compared to older forms of medication, there is less risk of tolerability and drug dependency associated with SSRIs.

Paroxetine and paroxetine CR, Sertraline, Escitalopram, Venlafaxine XR and Fluvoxamine CR (luvox CR) are all approved for SAD and are all effective for it, especially paroxetine. All SSRIs are somewhat effective for social anxiety except fluoxetine which was equivalent to placebo in all clinical trials except one. Paroxetine was able to change personality and significantly increase extraversion.

In a 1995 double-blind, placebo-controlled trial, the SSRI paroxetine was shown to result in clinically meaningful improvement in 55% of patients with generalized social anxiety disorder, compared with 23.9% of those taking placebo. An October 2004 study yielded similar results. Patients were treated with either fluoxetine, psychotherapy, or a placebo. The first four sets saw improvement in 50.8 to 54.2 percent of the patients. Of those assigned to receive only a placebo, 31.7% achieved a rating of 1 or 2 on the Clinical Global Impression-Improvement scale. Those who sought both therapy and medication did not see a boost in improvement. In double-blind, placebo-controlled trials other SSRIs like fluvoxamine, escitalopram and sertraline showed reduction of social anxiety symptoms, including anxiety, sensitivity to rejection and hostility.

Citalopram also appears to be effective.

General side-effects are common during the first weeks while the body adjusts to the drug. Symptoms may include headaches, nausea, insomnia and changes in sexual behavior. Treatment safety during pregnancy has not been established. In late 2004 much media attention was given to a proposed link between SSRI use and suicidality [a term that encompasses suicidal ideation and attempts at suicide as well as suicide]. For this reason, [although evidential causality between SSRI use and actual suicide has not been demonstrated] the use of SSRIs in pediatric cases of depression is now recognized by the Food and Drug Administration as warranting a cautionary statement to the parents of children who may be prescribed SSRIs by a family doctor. Recent studies have shown no increase in rates of suicide. These tests, however, represent those diagnosed with depression, not necessarily with social anxiety disorder.

In addition, studies show that more socially phobic patients treated with anti-depressant medication develop hypomania than non-phobic controls. The hypomania can be seen as the medication creating a new problem.

Other drugs

Other prescription drugs are also used, if other methods are not effective. Before the introduction of SSRIs, monoamine oxidase inhibitors (MAOIs) such as phenelzine were frequently used in the treatment of social anxiety. Evidence continues to indicate that MAOIs are effective in the treatment and management of social anxiety disorder and they are still used, but generally only as a last resort medication, owing to concerns about dietary restrictions, possible adverse drug interactions and a recommendation of multiple doses per day. A newer type of this medication, reversible inhibitors of monoamine oxidase subtype A (RIMAs) such as the drug moclobemide, bind reversibly to the MAO-A enzyme, greatly reducing the risk of hypertensive crisis with dietary tyramine intake. However, RIMAs have been found to be less efficacious for social anxiety disorder than irreversible MAOIs like phenelzine.

Benzodiazepines are an alternative to SSRIs. These drugs' recommended usage is for short-term relief, meaning a limited time frame of over a year, of severe, disabling anxiety. Although benzodiazepines are still sometimes prescribed for long-term everyday use in some countries, there is concern over the development of drug tolerance, dependency and misuse. It has been recommended that benzodiazepines be considered only for individuals who fail to respond to other medications. Benzodiazepines augment the action of GABA, the major inhibitory neurotransmitter in the brain; effects usually begin to appear within minutes or hours. In most patients, tolerance rapidly develops to the sedative effects of benzodiazepines, but not to the anxiolytic effects. Long-term use of a benzodiazepine may result in physical dependence, and abrupt discontinuation of the drug should be avoided due to high potential for withdrawal symptoms (including tremor, insomnia, and in rare cases, seizures). A gradual tapering of the dose of clonazepam (a decrease of 0.25 mg every 2 weeks), however, is well tolerated by patients with social anxiety disorder. Benzodiazepines are not recommended as monotherapy for patients who have major depression in addition to social anxiety disorder and should be avoided in patients with a history of substance use.

Certain anticonvulsant drugs such as gabapentin are effective in social anxiety disorder and may be a possible treatment alternative to benzodiazepines.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine have shown similar effectiveness to the SSRIs. In Japan, Milnacipran is used in the treatment of Taijin kyofusho, a Japanese variant of social anxiety disorder. The atypical antidepressants mirtazapine and bupropion have been studied for the treatment of social anxiety disorder, and rendered mixed results.

Some people with a form of social phobia called performance phobia have been helped by beta-blockers, which are more commonly used to control high blood pressure. Taken in low doses, they control the physical manifestation of anxiety and can be taken before a public performance.

A novel treatment approach has recently been developed as a result of translational research. It has been shown that a combination of acute dosing of d-cycloserine (DCS) with exposure therapy facilitates the effects of exposure therapy of social phobia. DCS is an old antibiotic medication used for treating tuberculosis and does not have any anxiolytic properties per se. However, it acts as an agonist at the glutamatergic N-methyl-D-aspartate (NMDA) receptor site, which is important for learning and memory.

Kava-kava has also attracted attention as a possible treatment, although safety concerns exist.

Epidemiology

Country	Prevalence
United States	2–7%
England	0.4% (children)
Scotland	1.8% (children)
Wales	0.6% (children)
Australia	1–2.7%
Brazil	4.7–7.9%
India	12.8% (adolescents)
Iran	0.8%
Israel	4.5%
Nigeria	9.4% (university students)
Sweden	15.6% (university students)
Turkey	9.6% (university students)
Poland	7–9% (2002)
Taiwan	7% children (2002~2008)

Social anxiety disorder is known to appear at an early age in most cases. Fifty percent of those who develop this disorder have developed it by the age of 11, and 80% have developed it by age 20. This early age of onset may lead to people with social anxiety disorder being particularly vulnerable to depressive illnesses, substance use, and other psychological conflicts.

When prevalence estimates were based on the examination of psychiatric clinic samples, social anxiety disorder was thought to be a relatively rare disorder. The opposite was found to be true; social anxiety was common, but many were afraid to seek psychiatric help, leading to an underrecognition of the problem.

The National Comorbidity Survey of over 8,000 American correspondents in 1994 revealed 12-month and lifetime prevalence rates of 7.9 percent and 13.3 percent, respectively; this makes it the third most prevalent psychiatric disorder after depression and alcohol use disorder, and the most common of the anxiety disorders. According to US epidemiological data from the National Institute of Mental Health, social phobia affects 15 million adult Americans in any given year. Estimates vary within 2 percent and 7 percent of the U.S. adult population.

The mean onset of social phobia is 10 to 13 years. Onset after age 25 is rare and is typically preceded by panic disorder or major depression. Social anxiety disorder occurs more often in females than males. The prevalence of social phobia appears to be increasing among white, married, and well-educated individuals. As a group, those with generalized social phobia are less likely to graduate from high school and are more likely to rely on government financial assistance or have poverty-level salaries. Surveys carried out in 2002 show the youth of England, Scotland, and Wales have a prevalence rate of 0.4 percent, 1.8 percent, and 0.6 percent, respectively. In Canada, the prevalence of self-reported social anxiety for Nova Scotians older than 14 years was 4.2 percent in June 2004 with women (4.6 percent) reporting more than men (3.8 percent). In Australia, social phobia is the 8th and 5th leading disease or illness for males and females between 15 and 24 years of age as of 2003. Because of the difficulty in separating social phobia from poor social skills or shyness, some studies have a large range of prevalence. The table also shows higher prevalence in Sweden.

Terminology

It has also been referred to as anthropophobia, meaning "fear of humans", from Greek: άνθρωπος, ánthropos, "human" and φόβος, phóbos, "fear". Other names have included interpersonal relation phobia. A specific Japanese cultural form is known as taijin kyofusho.