MDI is characterized by periods of deep,
prolonged, and profound depression that alternate
with periods of an excessively elevated or irritable
mood known as mania; with a normal period
(intermission) in between them.
Manic episodes are feature at least 1 week of profound mood disturbance, characterized by
elation, irritability, or expansiveness (referred to as gateway criteria). At least 3 of the following
symptoms must also be present.
Diminished need for sleep
Excessive talking or pressured speech
Racing thoughts or flight of ideas
Clear evidence of distractibility
Increased level of goal-focused activity
at home, at work, or sexually
Excessive pleasurable activities, often with
Hypomanic episodes are characterized by an elevated, expansive, or irritable mood of at least 4
consecutive days’ duration. At least 3 of the following symptoms are also present:
Grandiosity or inflated self-esteem
Diminished need for sleep
Racing thoughts or flight of ideas
Clear evidence of distractibility
Increased level of goal-focused activity
at home, at work, or sexually
Engaging in activities with a high potential
for painful consequences
MAJOR DEPRESSIVE EPISODES:
Major depressive episodes are characterized as, for the same 2 weeks, the person experiences
5 or more of the following symptoms, with at least 1 of the symptoms being either a depressed
mood or characterized by a loss of pleasure or interest:
Markedly diminished pleasure or interest
in nearly all activities
Significant weight loss or gain or significant
loss or increase in appetite
Hypersomnia or insomnia
Psychomotor retardation or agitation
Loss of energy or fatigue
Feelings of worthlessness or excessive guilt
Decreased concentration ability or marked
Preoccupation with death or suicide; patient
has a plan or has attempted suicide
Bipolar I disorder: involves periods of severe mood episodes from mania to depression.
Bipolar II disorder: is a milder form of mood elevation, involving milder episodes of hypomania that alternate
with periods of severe depression.
Cyclothymic disorder describes periods of hypomania with brief periods of depression that are not as
extensive or long-lasting as seen in full depressive episodes.
Mixed features: refers to the occurrence of simultaneous symptoms of opposite mood polarities during manic,
hypomanic or depressive episodes. It's marked by high energy, sleeplessness, and racing thoughts. At the same
time, the person may feel hopeless, despairing, irritable, and suicidal.
It is a term that describes having four or more mood episodes within a 12-month period. Episodes must last for
some minimum number of days in order to be considered distinct episodes. Some people also experience
changes in polarity from high to low or vice-versa within a single week, or even within a single day -- the full
symptom profile that defines distinct, separate episodes may not be present (for example, the person may not
have a decreased need for sleep), making such "ultra-rapid" cycling a more controversial phenomenon.
Rapid cycling can occur at any time in the course of illness, although some researchers believe that it may be
more common at later points in the lifetime duration of illness.
Women appear more likely than men to have rapid cycling. A rapid-cycling pattern increases risk for severe
depression and suicide attempts.
Antidepressants may sometimes be associated with triggering or prolonging periods of rapid cycling.
A number of factors contribute to bipolar affective disorder, or manic-depressive illness (MDI),
including genetic, biochemical, psychodynamic, and environmental factors.
Bipolar disorder, especially bipolar type I (BPI) disorder, has a major genetic
component, with the involvement of the ANK3,CACNA1C, and CLOCK genes.
First-degree relatives of people with BPI are approximately 7 times more likely to
develop BPI than the general population. Remarkably, offspring of a parent with
bipolar disorder have a 50% chance of having another major psychiatric disorder.
Gene expression studies also demonstrate that persons with bipolar disorder, major
depression, and schizophrenia share similar decreases in the expression of
oligodendrocyte-myelin-related genes and abnormalities of white matter in various
A meta-analysis by Houenou et al found :
Decreased activation and diminution of gray matter in a cortical-cognitive brain network, which has
been associated with the regulation of emotions in patients with bipolar disorder.
An increased activation in ventral limbic brain regions that mediate the experience of emotions and
generation of emotional responses .
This provides evidence for functional and anatomic alterations in bipolar disorder in brain networks associated
with the experience and regulation of emotions.
Many practitioners see the depression as the manifestation of losses (ie, the loss of self-esteem and the sense of
worthlessness).Therefore, the mania serves as a defence against the feelings of depression. Melanie Klein was one
of the major proponents of this formulation.
A study by Barnett et al found that personality disturbances in extraversion, neuroticism, and openness are often
noted in patients with bipolar disorder and may be enduring characteristics.
External stresses or the external pressures may serve to exacerbate some underlying genetic or biochemical
For example, Pregnancy is a particular stress for women with a manic-depressive illness history and increases the
possibility of postpartum psychosis.
Because of the nature of their work, certain individuals have periods of high demands followed by periods of few
For example, a landscaper and gardener who was busy in the spring, summer, and fall became relatively inactive
during the winter, except for plowing snow. Consequently, he appeared manic for a good part of the year, and then
he would crash and hibernate during the cold months
A number of neurotransmitters have been linked to this disorder, largely based on patients’ responses to
psychoactive agents as in the following examples.
The blood pressure drug reserpine, which depletes catecholamines from nerve terminals, was noted incidentally
to cause depression. This led to the catecholamine hypothesis, which holds that an increase in epinephrine and
norepinephrine causes mania and a decrease in epinephrine and norepinephrine causes depression.
Drugs used to treat depression and drugs of abuse (eg, cocaine) that increase levels of monoamines, including
serotonin, norepinephrine, or dopamine, can all potentially trigger mania, implicating all of these
neurotransmitters in its etiology.
Other agents that exacerbate mania include L-dopa, which implicates dopamine and serotonin-reuptake inhibitors,
which in turn implicate serotonin.
Evidence is mounting of the contribution of glutamate to both bipolar disorder and major depression. A post-
mortem study of the frontal lobes of individuals with these disorders revealed that the glutamate levels were
Calcium channel blockers have been used to treat mania, which may also result from a disruption of intracellular
calcium regulation in neurons as suggested by experimental and genetic data. The proposed disruption of calcium
regulation may be caused by various neurologic insults, such as excessive glutaminergic transmission or ischemia.
Interestingly, valproate specifically upregulates expression of a calcium chaperone protein, GRP 78, which may be
one of its chief mechanisms of cellular protection.
Hormonal imbalances and disruptions of the hypothalamic-
pituitary-adrenal axis involved in homeostasis and the stress
response may also contribute to the clinical picture of bipolar
Examination of patients with suspected bipolar
Affective disorder includes evaluation using the
Mental Status Examination as well as assessment
of the following:
Persons experiencing a depressed episode may demonstrate poor to no eye contact. Their clothes may be
unkempt, unclean, holed, un ironed, and ill-fitting. If the person has lost significant weight, the garments may fit
Men: poor grooming, lack of shaving, and lack of washing, may exhibit dirty fingernails and hands.
Women: fingernails may show different layers of polish or one layer partially removed, and they may not have
paid attention to their hair.
They move slowly and very little; they show psychomotor retardation; they may talk in low tones or in a
depressed or monotone voice.
Persons experiencing a hypomanic episode are busy, active, and involved. They have energy and are always on the
go. They are always planning and doing things. Others notice their energy levels and mood changes.
Patients experiencing the manic phase are hyperactive and might be hypervigilant. They are restless, energized,
and active. They talk and act fast. Their attire also reflects the mania: Their clothes might have been put on in
haste and are disorganized. Alternately, their garments are often too bright, colorful, or garish. These individuals
stand out in a crowd, because their dress frequently attracts attention.
In persons experiencing a depressed episode, sadness
dominates the affect. These individuals feel sad, depressed,
lost, vacant, and isolated. The "2 Hs"— hopeless
and helpless—often accompany their mood. When in the
presence of such patients, one comes away feeling sad and
In persons experiencing a hypomanic episode, the mood is up,
expansive, and often irritable.
In persons experiencing a manic episode, the mood is
inappropriately joyous, elated, and jubilant. These individuals
are euphoric. They also may demonstrate annoyance and
irritability, especially if the mania has been present for a
significant length of time.
Persons experiencing a mixed episode exhibit both depression
and mania within a brief period (≤1 wk).
Patients experiencing a depressed episode have thoughts that reflect their sadness. They are preoccupied
with negative ideas and nihilistic concerns.
Patients experiencing a hypomanic episode are optimistic, forward thinking, and have a positive attitude.
Patients experiencing a manic episode have very expansive and optimistic thinking. They may be excessively
self-confident or grandiose, often have a very rapid production of ideas and thoughts, perceive their minds
as being very active, and see themselves as being highly engaging and creative. These individuals are highly
distractible and quickly shift from one person to another.
Patients experiencing a mixed episode can oscillate dramatically between depression and euphoria, and they
often demonstrate marked irritability.
In persons experiencing a depressive episode, the depression clouds and dims their judgment and colors their
insights. They fail to make important plans/actions, because they are so down and preoccupied with their own
These individuals see no tomorrow; therefore, planning for it is difficult. Frequently, persons in the middle of a
depression have done things such as forgetting to pay their income taxes. At that time, they have little insight into
their behavior. Often, others have to persuade them to seek therapy because of their lack of insight.
Persons experiencing a hypomanic episode generally act expansively and may demonstrate poor judgment by
taking on too many tasks or becoming overinvolved. Often, their distractibility impairs their judgment, and they
have little insight into their driven qualities. They see themselves as productive and conscientious, not as
In patients experiencing a manic episode, judgment is seriously impaired. These persons make terrible decisions in
their work and family.
For eg: they may invest the family fortune in very questionable programs, become professionally over involved in
work activities or with coworkers, or start dramatically unsound fiscal or professional ventures. These individuals
ignore feedback, suggestions, and advice from friends, family, and colleagues. They have no insight into the
extreme nature of their demands, plans, and behavior. Often, commitment proves the only way to contain them.
In persons experiencing a mixed episode, major shifts in affect during short lengths of time severely impair their
judgment and interfere with their insight.
Two forms of a major depression are described, one with psychotic features and the other without.
With psychosis, the patient experiences delusions and hallucinations that are either consistent or inconsistent
with the mood.
The patient’s delusions of having sinned are accompanied by guilt and remorse, or the patient feels he or she is
utterly worthless and should live in total deprivation and degradation. Hence, the delusional content remains
consistent with the depressed mood. Some patients experience delusions that are inconsistent with the
depression, such as paranoia or persecutory delusions.
By definition, patients experiencing a hypomanic episode do not experience hallucinations.
Approximately three fourths of patients experiencing a manic episode have delusions. As in major depression,
the delusional content is either consistent or inconsistent with the mania. Manic delusions reflect perceptions
of power, prestige, position, self-worth, and glory.
Patients experiencing a mixed episode might exhibit delusions and hallucinations consistent with either
depression or mania or congruent to both.
Impairments in orientation and memory are seldom observed in patients with bipolar disorder unless they are
They know the time and their location, and they recognize people. They can remember immediate, recent, and
distant events. In some cases of hypomanic and even manic episodes, their ability to recall information can be
extremely vivid and expanded.
However, later in the course of their illness, their cognition becomes impaired.
In extremes of depression and mania, these individuals may experience difficulty in concentrating and focusing.
Similar to subcortical dementia, depression impairs cognition.
Patients with bipolar disorder have a high incidence of endocrine disorders, cardiovascular
disorders, and obesity,and these factors must be considered when medications are
The treatment of bipolar affective disorder is directly related to the phase of
the episode (ie, depression or mania) and the severity of that phase, and it
may involve a combination of psychotherapy and medication.
Always evaluate patients with mania, hypomania, or mixed episode, and those
with bipolar depression, for suicidality, acute or chronic psychosis, or other
unstable or dangerous conditions.
Medications used to manage patients with bipolar disorder include the following:
Benzodiazepines (eg, lorazepam, clonazepam)
Antimanic agents (eg, lithium)
Anticonvulsants (eg, carbamazepine, valproate sodium,valproic acid, divalproex sodium, lamotrigine, topiramate)
First-generation antipsychotics (eg, inhaled loxapine, haloperidol)
Second-generation antipsychotics (eg, asenapine, ziprasidone, quetiapine, risperidone, aripiprazole, olanzapine, olanzapine
and fluoxetine, clozapine, paliperidone)
Phenothiazine antipsychotics (eg, chlorpromazine)
Dopamine agonists (eg, pramipexole)
Psychotherapy may help to decrease relapse rates, improve quality of life, and/or increase functioning, or
more favourable symptom improvement.
Patients with chronic medical illnesses and depression should be treated with a comprehensive approach involving
the patient, the family, the support team, the physician, other professionals, and community resources. Such
models, called Collaborative Chronic Care Models (CCMs), have been developed to improve outcomes in chronically
ill patients treated in the primary care setting who also suffer from depression.
CCMs were defined a priori as interventions with at least 3 of the 6 components of the Improving Chronic Illness
Care initiative, as follows:
Patient self-management support
Clinical information systems
Delivery system redesign
Community resource linkages
Electroconvulsive therapy: may be useful in selected patients with bipolar disorder. Especially,
When rapid, definitive medical/psychiatric treatment is needed
When the risks of ECT are less than that of other treatments
When the bipolar disorder is refractory to an adequate trial with other treatment strategies
When the patient prefers this treatment modality
Often, the severity of the patient’s symptoms, the lack of response to medications, or the presence of
contraindications to certain medications necessitates the use of ECT. This treatment modality has proven to be highly
effective in the treatment of acute mania.
INDICATIONS FOR INPATIENT MANAGEMENT:
Patients diagnosed with bipolar mania or depression and severe symptoms must be referred for urgent/emergent
mental health intervention. The indications for inpatient treatment in a person with bipolar affective disorder, or
manic-depressive illness (MDI), include the following:
•Danger to self
•Danger to others
•Marked psychotic symptoms
•Total inability to function
•Total loss of control (eg, excessive spending, undertaking a dangerous trip)
•Medical conditions that warrant medication monitoring (eg, substance withdrawal/intoxication
Factors suggesting a worse prognosis include the
•Poor job history
•Depressive features between periods of mania and
•Evidence of depression
•Pattern of depression-mania-euthymia
Factors suggesting a better prognosis include
•Length of manic phases (short duration)
•Late age of onset
•Few thoughts of suicide
•Few psychotic symptoms
•Few medical problems
LIFE STYLE MODIFICATIONS:
Patients in the depressed phase are encouraged to exercise. These individuals should try to develop a regular daily
schedule of major activities, especially times of going to bed and waking up.
Propose a regular exercise schedule for all patients, especially those with bipolar disorder. Both the exercise and
the regular schedule are keys to surviving this illness.
PREVENTION AND LONG TERM MONITORING:
Prevention is the key to the long-term treatment of bipolar affective
disorders, , or manic-depressive illness (MDI), as follows:
First, use medications such as lithium serve as mood stabilizers
Second, psycho education is instituted for the patient and the patient’s
family; it is critical that the patient and the patient’s family understand
and recognize the importance of medication compliance and the early
signs of mania and depression
Re evaluate for treatment response every 1-2 weeks for a minimum of 6 weeks.
Continue to monitor these individuals for the following situations:
•Depressive symptoms (or changes in), suicidal/homicide ideation
•Neuro vegetative symptoms
•New-onset/change in psychotic symptoms or manic/hypomanic symptoms
•Illicit substance use
•Medication side effects and compliance
•Significant psychosocial changes
Re evaluate all patients for treatment response at 4-8 weeks, after each change in treatment, and periodically until
full remission is achieved.
Full remission is defined in patients with mania as the absence of significant mania symptoms for 2 months; in
patients with mixed episode, it is the absence of significant mania or depression symptoms for 2 months; and in
those with bipolar depression, it is the absence of significant depressive symptoms for 2 months.
Treat adult patients who have had an acute manic episode for a minimum of 6 months after the initial episode is
controlled; encourage these individuals—as well as those who have had more than 1 manic episode or with 1 manic
and 1 depressive episode, or 3 or more depressive episodes—to continue on lifelong prophylactic pharmacotherapy.
Following full remission of the depressive episode, consider withdrawing antidepressant treatment after 4-6 months.
Discontinuation should consist of a gradual taper over a minimum 2-4–week period, unless medically