| Mania | |
|---|---|
| Other names | Manic syndrome, manic episode |
 | |
| Graphical representation of mania and hypomania | |
| Specialty | Psychiatry |
Mania, also known as manic syndrome, is a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together with lability of affect." Although mania is often conceived as a "mirror image" to depression, the heightened mood can be either euphoric or irritable; indeed, as the mania intensifies, irritability can be more pronounced and result in anxiety, or violence.
The symptoms of mania include elevated mood (either euphoric or irritable), flight of ideas and pressure of speech, increased energy, decreased need and desire for sleep, and hyperactivity. They are most plainly evident in fully developed hypomanic states. However, in full-blown mania, they undergo progressively severe exacerbations and become more and more obscured by other signs and symptoms, such as delusions and fragmentation of behavior.
Causes and Diagnosis
Mania is a syndrome with multiple causes. Although the vast majority of cases occur in the context of bipolar disorder, it is a key component of other psychiatric disorders (such as schizoaffective disorder, bipolar type) and may also occur secondary to various general medical conditions, such as multiple sclerosis; certain medications may perpetuate a manic state, for example prednisone; or substances prone to abuse, especially stimulants, such as caffeine and cocaine. In the current DSM-5,
hypomanic episodes are separated from the more severe full manic
episodes, which, in turn, are characterized as either mild, moderate, or
severe, with certain diagnostic criteria (e.g. catatonia, psychosis). Mania is divided into three stages: hypomania, or stage I; acute mania, or stage II; and delirious mania (delirium), or stage III. This "staging" of a manic episode is useful from a descriptive and differential diagnostic point of view.
Mania varies in intensity, from mild mania (hypomania) to delirious mania, marked by such symptoms as disorientation, florid psychosis, incoherence, and catatonia. Standardized tools such as Altman Self-Rating Mania Scale and Young Mania Rating Scale can be used to measure severity of manic episodes. Because mania and hypomania have also long been associated with creativity and artistic talent,
it is not always the case that the clearly manic/hypomanic bipolar
patient needs or wants medical help; such persons often either retain
sufficient self-control to function normally or are unaware that they
have "gone manic" severely enough to be committed or to commit themselves. Manic persons often can be mistaken for being under the influence of drugs.
Classification
Mixed states
In a mixed affective state, the individual, though meeting the general criteria for a hypomanic (discussed below) or manic episode, experiences three or more concurrent depressive
symptoms. This has caused some speculation, among clinicians, that
mania and depression, rather than constituting "true" polar opposites,
are, rather, two independent axes in a unipolar—bipolar spectrum.
A mixed affective state, especially with prominent manic symptoms, places the patient at a greater risk for completed suicide. Depression
on its own is a risk factor but, when coupled with an increase in
energy and goal-directed activity, the patient is far more likely to act
with violence on suicidal impulses.
Associated disorders
A
single manic episode, in the absence of secondary causes, (i.e.,
substance use disorders, pharmacologics, or general medical conditions)
is often sufficient to diagnose bipolar I disorder. Hypomania may be indicative of bipolar II disorder.
Manic episodes are often complicated by delusions and/or
hallucinations; and if the psychotic features persist for a duration
significantly longer than the episode of typical mania (two weeks or
more), a diagnosis of schizoaffective disorder is more appropriate. Certain obsessive-compulsive spectrum disorders as well as impulse control disorders share the suffix "-mania," namely, kleptomania, pyromania, and trichotillomania. Despite the unfortunate association implied by the name, however, no connection exists between mania or bipolar disorder and these disorders.
Furthermore, evidence indicates a B12 deficiency can also cause symptoms characteristic of mania and psychosis.
Hyperthyroidism
can produce similar symptoms to those of mania, such as agitation,
elevated mood, increased energy, hyperactivity, sleep disturbances and
sometimes, especially in severe cases, psychosis.
Signs and symptoms
A manic episode is defined in the American Psychiatric Association's diagnostic manual
as a "distinct period of abnormally and persistently elevated,
expansive, or irritable mood and abnormally and persistently increased
activity or energy, lasting at least 1 week and present most of the day,
nearly every day (or any duration, if hospitalization is necessary)," where the mood is not caused by drugs/medication or a non-mental medical illness (e.g., hyperthyroidism),
and: (a) is causing obvious difficulties at work or in social
relationships and activities, or (b) requires admission to hospital to
protect the person or others, or (c) the person is suffering psychosis.
To be classified as a manic episode, while the disturbed mood and
an increase in goal directed activity or energy is present, at least
three (or four, if only irritability is present) of the following must
have been consistently present:
- Inflated self-esteem or grandiosity.
- Decreased need for sleep (e.g., feels rested after 3 hours of sleep).
- More talkative than usual, or acts pressured to keep talking.
- Flights of ideas or subjective experience that thoughts are racing.
- Increase in goal directed activity, or psychomotor acceleration.
- Distractibility (too easily drawn to unimportant or irrelevant external stimuli).
- Excessive involvement in activities with a high likelihood of painful consequences.(e.g., extravagant shopping, improbable commercial schemes, hypersexuality).
Though the activities one participates in while in a manic state are not always negative, those with the potential to have negative outcomes are far more likely.
If the person is concurrently depressed, they are said to be having a mixed episode.
The World Health Organization's classification system defines a manic episode
as one where mood is higher than the person's situation warrants and
may vary from relaxed high spirits to barely controllable exuberance, is
accompanied by hyperactivity, a compulsion to speak, a reduced sleep
requirement, difficulty sustaining attention and/or often increased
distractibility. Frequently, confidence and self-esteem are excessively
enlarged, and grand, extravagant ideas are expressed. Behavior that is
out of character and risky, foolish or inappropriate may result from a
loss of normal social restraint.
Some people also have physical symptoms, such as sweating,
pacing, and weight loss. In full-blown mania, often the manic person
will feel as though his or her goal(s) are of paramount importance, that
there are no consequences or that negative consequences would be
minimal, and that they need not exercise restraint in the pursuit of
what they are after. Hypomania
is different, as it may cause little or no impairment in function. The
hypomanic person's connection with the external world, and its
standards of interaction, remain intact, although intensity of moods is
heightened. But those who suffer from prolonged unresolved hypomania do
run the risk of developing full mania, and indeed may cross that "line"
without even realizing they have done so.
One of the signature symptoms of mania (and to a lesser extent, hypomania) is what many have described as racing thoughts. These are usually instances in which the manic person is excessively distracted by objectively unimportant stimuli.
This experience creates an absent-mindedness where the manic
individual's thoughts totally preoccupy him or her, making him or her
unable to keep track of time, or be aware of anything besides the flow
of thoughts. Racing thoughts also interfere with the ability to fall
asleep.
Manic states are always relative to the normal state of intensity
of the afflicted individual; thus, already irritable patients may find
themselves losing their tempers even more quickly, and an academically
gifted person may, during the hypomanic stage, adopt seemingly "genius"
characteristics and an ability to perform and articulate at a level far
beyond that which they would be capable of during euthymia.
A very simple indicator of a manic state would be if a heretofore
clinically depressed patient suddenly becomes inordinately energetic,
enthusiastic, cheerful, aggressive, or "over happy". Other, often less
obvious, elements of mania include delusions (generally of either
grandeur or persecution, according to whether the predominant mood is
euphoric or irritable), hypersensitivity, hypervigilance,
hypersexuality, hyper-religiosity, hyperactivity and impulsivity, a
compulsion to over explain (typically accompanied by pressure of
speech), grandiose schemes and ideas, and a decreased need for sleep
(for example, feeling rested after only 3 or 4 hours of sleep). In the
case of the latter, the eyes of such patients may both look and seem
abnormally "wide open", rarely blinking, and may contribute to some
clinicians’ erroneous belief that these patients are under the influence
of a stimulant drug, when the patient, in fact, is either not on any
mind-altering substances or is actually on a depressant drug.
Individuals may also engage in out-of-character behavior during the
episode, such as questionable business transactions, wasteful
expenditures of money (e.g., spending sprees), risky sexual activity,
abuse of recreational substances, excessive gambling, reckless behavior
(such as extreme speeding or other daredevil activity), abnormal social
interaction (e.g. over familiarity and conversing with strangers), or
highly vocal arguments. These behaviours may increase stress in personal
relationships, lead to problems at work, and increase the risk of
altercations with law enforcement. There is a high risk of impulsively
taking part in activities potentially harmful to the self and others.
Although "severely elevated mood" sounds somewhat desirable and
enjoyable, the experience of mania is ultimately often quite unpleasant
and sometimes disturbing, if not frightening, for the person involved
and for those close to them, and it may lead to impulsive behaviour that
may later be regretted. It can also often be complicated by the
sufferer's lack of judgment and insight regarding periods of
exacerbation of characteristic states. Manic patients are frequently
grandiose, obsessive, impulsive, irritable, belligerent, and frequently
deny anything is wrong with them. Because mania frequently encourages
high energy and decreased perception of need or ability to sleep, within
a few days of a manic cycle, sleep-deprived psychosis
may appear, further complicating the ability to think clearly. Racing
thoughts and misperceptions lead to frustration and decreased ability to
communicate with others.
Mania may also, as earlier mentioned, be divided into three
“stages”. Stage I corresponds with hypomania and may feature typical
hypomanic characteristics, such as gregariousness and euphoria. In stages II and III mania, however, the patient may be extraordinarily irritable, psychotic or even delirious. These latter two stages are referred to as acute and delirious (or Bell's), respectively.
Cause
Various triggers have been associated with switching from euthymic
or depressed states into mania. One common trigger of mania is
antidepressant therapy. Studies show that the risk of switching while
on an antidepressant is between 6-69 percent. Dopaminergic drugs such
as reuptake inhibitors and dopamine agonists may also increase risk of
switch. Other medication possibly include glutaminergic agents and
drugs that alter the HPA axis.
Lifestyle triggers include irregular sleep-wake schedules and sleep
deprivation, as well as extremely emotional or stressful stimuli.
Various genes that have been implicated in genetic studies of
bipolar have been manipulated in preclinical animal models to produce
syndromes reflecting different aspects of mania. CLOCK and DBP
polymorphisms have been linked to bipolar in population studies, and
behavioral changes induced by knockout are reversed by lithium
treatment. Metabotropic glutamate receptor 6 has been genetically linked to bipolar, and found to be under-expressed in the cortex. Pituitary adenylate cyclase-activating peptide
has been associated with bipolar in gene linkage studies, and knockout
in mice produces mania like-behavior. Targets of various treatments such
as GSK-3, and ERK1 have also demonstrated mania like behavior in preclinical models.
Mania may be associated with strokes, especially cerebral lesions in the right hemisphere.
Deep brain stimulation of the subthalamic nucleus in Parkinson's disease has been associated with mania, especially with electrodes placed in the ventromedial STN. A proposed mechanism involves increased excitatory input from the STN to dopaminergic nuclei.
Mania can also be caused by physical trauma or illness. When the causes are physical, it is called secondary mania.
Mechanism
The mechanism underlying mania is unknown, but the neurocognitive
profile of mania is highly consistent with dysfunction in the right
prefrontal cortex, a common finding in neuroimaging studies. Various lines of evidence from post-mortem studies and the putative mechanisms of anti-manic agents point to abnormalities in GSK-3, dopamine, Protein kinase C and Inositol monophosphatase.
Meta analysis of neuroimaging studies demonstrate increased
thalamic activity, and bilaterally reduced inferior frontal gyrus
activation. Activity in the amygdala and other subcortical structures such as the ventral striatum
tend to be increased, although results are inconsistent and likely
dependent upon task characteristics such as valence. Reduced functional
connectivity between the ventral prefrontal cortex and amygdala along with variable findings supports a hypothesis of general dysregulation of subcortical structures by the prefrontal cortex. A bias towards positively valenced stimuli, and increased responsiveness in reward circuitry may predispose towards mania.
Mania tends to be associated with right hemisphere lesions, while
depression tends to be associated with left hemisphere lesions.
Post-mortem examinations of bipolar disorder demonstrate increased expression of Protein Kinase C (PKC).
While limited, some studies demonstrate manipulation of PKC in animals
produces behavioral changes mirroring mania, and treatment with PKC
inhibitor tamoxifen
(also an anti-estrogen drug) demonstrates antimanic effects.
Traditional antimanic drugs also demonstrate PKC inhibiting properties,
among other effects such as GSK3 inhibition.
Manic episodes may be triggered by dopamine receptor agonists, and this combined with tentative reports of increased VMAT2 activity, measured via PET scans of radioligand binding, suggests
a role of dopamine in mania. Decreased cerebrospinal fluid levels of the serotonin metabolite 5-HIAA
have been found in manic patients too, which may be explained by a
failure of serotonergic regulation and dopaminergic hyperactivity.
Limited evidence suggests that mania is associated with
behavioral reward hypersensitivity, as well as with neural reward
hypersensitivity. Electrophysiological evidence supporting this comes
from studies associating left frontal EEG activity with mania. As left frontal EEG activity is generally thought to be a reflection of behavioral activation system
activity, this is thought to support a role for reward hypersensitivity
in mania. Tentative evidence also comes from one study that reported
an association between manic traits and feedback negativity during
receipt of monetary reward or loss. Neuroimaging evidence during acute
mania is sparse, but one study reported elevated orbitofrontal cortex
activity to monetary reward, and another study reported elevated
striatal activity to reward omission. The latter finding was
interpreted in the context of either elevated baseline activity
(resulting in a null finding of reward hypersensitivity), or reduced
ability to discriminate between reward and punishment, still supporting
reward hyperactivity in mania.
Punishment hyposensitivity, as reflected in a number of neuroimaging
studies as reduced lateral orbitofrontal response to punishment, has
been proposed as a mechanism of reward hypersensitivity in mania.
Diagnosis
In the ICD-10 there are several disorders with the manic syndrome: organic manic disorder (F06.30), mania without psychotic symptoms (F30.1), mania with psychotic symptoms (F30.2), other manic episodes (F30.8), unspecified manic episode (F30.9), manic type of schizoaffective disorder (F25.0), bipolar affective disorder, current episode manic without psychotic symptoms (F31.1), bipolar affective disorder, current episode manic with psychotic symptoms (F31.2).
Treatment
Before beginning treatment for mania, careful differential diagnosis must be performed to rule out secondary causes.
The acute treatment of a manic episode of bipolar disorder involves the utilization of either a mood stabilizer (valproate, lithium, lamotrigine, or carbamazepine) or an atypical antipsychotic (olanzapine, quetiapine, risperidone, or aripiprazole). Although hypomanic
episodes may respond to a mood stabilizer alone, full-blown episodes
are treated with an atypical antipsychotic (often in conjunction with a
mood stabilizer, as these tend to produce the most rapid improvement).
When the manic behaviours have gone, long-term treatment then focuses on prophylactic treatment to try to stabilize the patient's mood, typically through a combination of pharmacotherapy and psychotherapy.
The likelihood of having a relapse is very high for those who have
experienced two or more episodes of mania or depression. While
medication for bipolar disorder is important to manage symptoms of mania
and depression, studies show relying on medications alone is not the
most effective method of treatment. Medication is most effective when
used in combination with other bipolar disorder treatments, including psychotherapy, self-help coping strategies, and healthy lifestyle choices.
Lithium
is the classic mood stabilizer to prevent further manic and depressive
episodes. A systematic review found that long term lithium treatment
substantially reduces the risk of bipolar manic relapse, by 42%. Anticonvulsants such as valproate, oxcarbazepine and carbamazepine are also used for prophylaxis. More recent drug solutions include lamotrigine and topiramate, both anticonvulsants as well.
In some cases, long-acting benzodiazepines, particularly clonazepam, are used after other options are exhausted. In more urgent circumstances, such as in emergency rooms, lorazepam
has been used to promptly alleviate symptoms of agitation, aggression,
and psychosis. Sometimes atypical antipsychotics are used in
combination with the previous mentioned medications as well, including olanzapine which helps treat hallucinations or delusions, asenapine, aripiprazole, risperidone, ziprasidone, and clozapine which is often used for people who do not respond to lithium or anticonvulsants.
Verapamil,
a calcium-channel blocker, is useful in the treatment of hypomania and
in those cases where lithium and mood stabilizers are contraindicated
or ineffective. Verapamil is effective for both short-term and long-term treatment.
Antidepressant monotherapy is not recommended for the treatment
of depression in patients with bipolar disorders I or II, and no benefit
has been demonstrated by combining antidepressants with mood
stabilizers in these patients. Some atypical antidepressants, however,
such as mirtazepine and trazodone have been occasionally used after other options have failed.
Society and culture
In Electroboy: A Memoir of Mania by Andy Behrman,
he describes his experience of mania as "the most perfect prescription
glasses with which to see the world... life appears in front of you like
an oversized movie screen".
Behrman indicates early in his memoir that he sees himself not as a
person suffering from an uncontrollable disabling illness, but as a
director of the movie that is his vivid and emotionally alive life.
There is some evidence that people in the creative industries suffer
from bipolar disorder more often than those in other occupations.
Winston Churchill had periods of manic symptoms that may have been both an asset and a liability.
English actor Stephen Fry, who suffers from bipolar disorder,
recounts manic behaviour during his adolescence: "When I was about 17
... going around London on two stolen credit cards, it was a sort of
fantastic reinvention of myself, an attempt to. I bought ridiculous
suits with stiff collars and silk ties from the 1920s, and would go to
the Savoy and Ritz and drink cocktails." While he has experienced suicidal thoughts, he says the manic side of his condition has had positive contributions on his life.
Etymology
The nosology of the various stages of a manic episode has changed over the decades. The word derives from the Ancient Greek μανία (manía), "madness, frenzy" and the verb μαίνομαι (maínomai), "to be mad, to rage, to be furious".
