Bipolar Affective Disorder - Symptoms

Bipolar disorder begins with an acute phase of symptoms, followed by cycles of exacerbations and remissions. Exacerbations are episodes with more severe symptoms, lasting from 3 to 6 months. Episodes may be manic, depressive, hypomanic, or mixed (symptoms of depression and mania). Cycles are the periods of time from the onset of one episode to the next, and vary in length. Cycling is particularly exacerbated in rapid-cycling bipolar disorder (usually defined as >4 episodes per year). Developmental and social problems are common, especially if the illness begins between the ages of 13 and 18.

Psychotic symptoms may be present. In full-blown manic psychosis, the mood is usually elevated, but irritability, open hostility and pickiness are often present.

Symptoms characteristic of bipolar disorder may be observed in many other diseases. Without excluding these conditions, correct diagnosis and adequate therapy are impossible. Bipolar disorder should be differentiated from affective disorders caused by somatic or neurological diseases, substance abuse, major depression, dysthymia and cyclothymia, psychotic disorders. In addition, obsessive-compulsive disorder with multiple compulsions can imitate pathologically purposeful actions in bipolar affective disorder. Affective lability in patients with borderline personality disorder may also resemble some features of bipolar affective disorder. In young patients, depression may be the first affective episode, which will subsequently develop into bipolar affective disorder. According to DSM-IV, the diagnosis of mania takes into account the duration and nature of symptoms, the degree of their impact on the patient's daily life, the presence of other causes that can explain this condition (general diseases, substance abuse, drug exposure).

List of commonly used drugs that are substrates of cytochrome P450 isoenzymes 1A2, 2C, 2D6 or 3A

1A2

• Antidepressants: tertiary tricyclic antidepressants, fluvoxamine
• Neuroleptics: clotapine, haloperidol, olanzapine, thioxanthenes, phenothiazides. Others: caffeine, theophylline, tacrine, verapamil, acetaminophen

2C

• Antidepressants: amitriptyline, imipramine, clomipramine, moclobemide, citalopram. Others: hexobarbital, diazepam, phenytoin, tolbutamide

2D6

• Antidepressants: amitriptyline, desipramine, imipramine, clomipramine, nortriptyline, trazodone, sertraline, fluoxetine, paroxetine, venlafaxine
• Neuroleptics: chlorpromazine, clozapine, perphenazine, haloperidol, risperndone, gioridazine, olanzapine
• Antiarrhythmics: encainide, flecainide, propafenone, mexiletine
• Beta blockers: labetalol, metoprolol, propranolol, timolol
• Opioids: codeine, hydrocodone, oxycodone
• Protease inhibitors: ritonavir
• Others: dextromethorphan, amphetamine, diphenhydramine, loratadine
• Benzodiazepines: alprazolam, clonazepam, midazolam, triazolam, diazepam
• Antihistamines: astemizole, terfenadine, loratadine
• Calcium antagonists: diltiazem, felodipine, nifedipine, verapamil
• Antidepressants: tertiary tricyclic antidepressants, nefazodone, sertraline, venlafaxine
• Antiarrhythmics, amiodarone, disopyramide, lidocaine, quinidine
• Protease inhibitors: ritonavir, indinavir, saquinavir
• Others: clozapine, carbamazepine, cisapride, dexamethasone, cyclosporine, cocaine, tamoxifen, estradiol, macrolide antibiotics

Some drugs, such as tertiary tricyclic antidepressants or clozapine, are metabolized through multiple pathways.

Bipolar affective disorder differs from unipolar affective disorder by the presence of different phases: mania, hypomania, and depression. The clinical picture of an episode of mania includes the following: elevated mood, verbal agitation, accelerated thinking, increased physical and mental activity, a surge of energy (with a decreased need for sleep), irritability, a particular vividness of sensations, paranoid ideas, hypersexuality, impulsivity.

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Mania (manic episode)

A manic episode is defined as 1 week or more of persistently elevated, uncontrollable, or irritable mood, accompanied by 3 or more additional symptoms, including: exaggerated self-esteem or grandiosity, decreased need for sleep, talkativeness, persistently elevated mood, flight of ideas or racing thoughts, increased distractibility, increased goal-directed activity, excessive involvement in pleasurable activities with a high risk of undesirable consequences (e.g., injury, spending money). The symptoms impair functioning.

Typically, patients in a manic state dress brightly, flashily, and colorfully; they behave in an authoritarian manner, and their speech is accelerated. The patient establishes associations by consonance: new thoughts are evoked by the sound of words, not by their meaning. Easily distracted patients may constantly switch from one topic or activity to another. However, they tend to believe that they are in an excellent mental state. Decreased criticism and increased activity often lead to intrusive behavior and can be a dangerous combination. Interpersonal disagreements develop, which can lead to paranoid ideas about unfair treatment and persecution. Accelerated mental activity is perceived by the patient as an acceleration of thoughts; the physician may observe a race of ideas, which in extreme manifestations is difficult to differentiate from the disruption of associative connections in schizophrenia. Some patients with bipolar I disorder develop psychotic symptoms. The need for sleep is reduced. Manic patients are inexhaustibly, excessively, and impulsively involved in various activities without recognizing the social danger inherent in them.

Diagnostic criteria for a manic episode

• A clearly defined period of excessive or persistently elevated mood, expansiveness, or irritability that persists for at least 1 week (or requires hospitalization, regardless of duration)
• During the period of mood disturbance, at least three (if mood changes are limited to irritability, but at least four) of the following symptoms are persistently present, and their severity reaches a significant degree:
• Inflated self-esteem, an exaggerated sense of one's own importance
• Reduced need for sleep (3 hours of sleep is enough to feel fully rested)
• Unusual talkativeness or a constant need to talk
• A rush of ideas or a subjective feeling of being overwhelmed by thoughts
• Distraction (attention is easily switched to irrelevant or random external stimuli)
• Increased goal-directed activity (social, at work or school, sexual) or psychomotor agitation
• Excessive involvement in pleasurable activities despite the high likelihood of unpleasant consequences (e.g., engaging in heavy drinking, promiscuous sexual activity, or poor financial investments)
• Symptoms do not meet criteria for a mixed episode
• The affective disorder is so severe that it significantly disrupts the patient's professional activity, or his usual social activity, or his relationships with other people, or requires hospitalization due to the danger of his actions to himself or others, or psychotic symptoms are revealed.
• The presenting symptoms are not caused by the direct physiological action of exogenous substances (including addictive substances or drugs) or general diseases (e.g. thyrotoxicosis)

According to DSM-IV, bipolar disorder is further classified by clinical characteristics. Thus, according to DSM-IV, there are bipolar disorder type I with a single (recent or current) manic (hypomanic, mixed, depressive, or unspecified) episode; bipolar disorder type II with a current or recent hypomanic or depressive episode; cyclothymia. In addition, according to DSM-IV, two aspects related to the course of the disorder should be clarified, namely: whether there is complete recovery between episodes or not, and whether there are seasonal patterns in the development of depressive episodes or rapid phase changes.

The severity of mania can vary widely.

Carlson and Goodwin (1973) identified the following stages (severities) of mania.

• Stage I. Increased psychomotor activity, affective lability, lack of restraint, exaggerated sense of self-importance, excessive self-confidence, sexual preoccupation; criticism is retained.
• Stage II. Speech and psychomotor agitation, pronounced depressive or dysphoric manifestations, open hostility, flight of ideas, paranoid delusions or delusions of grandeur.
• Stage III. Despair, panic attacks, feelings of hopelessness, violent and inappropriate actions, fragmented and incoherent thinking, hallucinations.

According to other terminology, there are variants such that stage I corresponds to hypomania, stage II - to mania, stage III - to delirious mania. Differential diagnostics of stage III of bipolar disorder and schizophrenia is often difficult if there is no additional source of information about the patient.

Mixed or dysphoric form of mania

Mixed or dysphoric mania is relatively common but less well understood than other forms of bipolar disorder. Mixed mania is found in 40-50% of hospitalized patients with bipolar disorder. According to DSM-IV, mixed mania is characterized by affective lability and a combination of manic and depressive symptoms that occur almost daily for at least 1 week. A mixed episode may be closely related in time to a depressive episode. Since the prognosis for mixed mania is less favorable than for "pure" mania, its recognition is important for determining therapy - anticonvulsants are more effective than lithium in treating this variant of bipolar disorder.

A mixed episode combines features of depression and mania or hypomania. The most typical examples are a momentary transition to tearfulness at the height of mania or a flight of ideas during the depressive period. In at least 1/3 of patients with bipolar disorder, the entire episode is mixed. The most common manifestations are dysphoric elation, tearfulness, shortened sleep, a flight of ideas, ideas of grandeur, psychomotor restlessness, suicidal ideation, persecutory delusions, auditory hallucinations, indecisiveness and confusion. This condition is called dysphoric mania (i.e., pronounced depressive symptoms are superimposed on manic psychosis).

Short Cycling Bipolar Disorder

Each episode of mania, depression, or hypomania is considered a separate episode. Short (rapid) cycles are observed in 1-20% of patients with bipolar disorder, and in 20% of cases this course occurs from the very beginning of the disease, and in 80% of cases it develops later. Short cycles are more often observed in women, and in most cases they begin with a depressive episode. In some patients, short cycles alternate with long ones. As in the case of mixed mania, recognition of this form is important for choosing treatment.

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Bipolar II disorder

Bipolar II disorder is characterized by episodes of hypomania and depression. Diagnosis is often complicated by overlapping personality traits, as well as the fact that the patient feels cheerful, energetic, and optimistic during a hypomanic episode and seeks medical help only when this condition gives way to depression. In addition, when these patients seek medical help during a depressive phase, they often cannot accurately describe their condition during the preceding hypomanic episode.

The difference between mania and hypomania is only in the degree of mental disturbances. Hypomanic disturbances are so minimal that they are often not considered by the patient as pathology. In this regard, it is important to obtain information about the patient from an additional source of information. Nevertheless, many patients note changes in criticism during hypomanic episodes, which could have serious consequences. The average age of onset of bipolar affective disorder type II is approximately 32 years. Thus, it occupies an intermediate position between bipolar affective disorder type I and unipolar depression. The number of episodes of affective disturbances in bipolar affective disorder type II is greater than in unipolar depression, and the duration of the cycle (i.e., the time from the beginning of one episode to the beginning of the next) in bipolar affective disorder type II is longer than in bipolar affective disorder type I.

If the patient is in a depressive phase, then the following factors support the diagnosis of bipolar affective disorder type II: early age of onset of the disease, presence of bipolar disorder in close relatives, effectiveness of lithium preparations in previous episodes, high frequency of episodes, drug induction of hypomania.

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Hypomania

A hypomanic episode is a discrete episode lasting 4 days or more that is distinctly different from the patient's usual mood when not depressed. The episode is characterized by 4 or more of the symptoms that occur during a manic episode, but the symptoms are less intense so that functioning is not significantly impaired.

Diagnostic criteria for hypomanic episode

• A clearly defined period of persistently elevated mood, expansiveness, or irritability that is distinctly different from the patient's usual normal (non-depressive) mood and that persists for at least 4 days
• During a period of mood disturbance, at least three (if mood changes are limited to irritability, then at least four) of the symptoms listed below are persistently present, and their severity reaches a significant degree:
• Inflated self-esteem, an exaggerated sense of one's own importance
• Reduced need for sleep (3 hours of sleep is enough to feel fully rested)
• Unusual talkativeness or a constant need to talk
• A rush of ideas or a subjective feeling of being overwhelmed by thoughts
• Distractibility (attention is easily switched to irrelevant or random external stimuli)
• Increased goal-directed activity (social, at work or school, sexual) or psychomotor agitation
• Excessive involvement in pleasurable activities despite the high likelihood of unpleasant consequences (e.g., engaging in heavy drinking, promiscuous sexual activity, or poor financial investments)
• The episode is accompanied by a clear change in the patient's life activity, which is not typical for him in the absence of symptoms. The mood disorder and change in the patient's life activity are noticeable to others.
• The disorder is not so severe as to significantly disrupt the patient's professional activities or social activity, does not require hospitalization, and is accompanied by psychotic symptoms.
• The presenting symptoms are not caused by the direct physiological action of exogenous substances (including addictive substances or drugs) or general diseases (e.g. thyrotoxicosis)

Cyclothymia

Cyclothymia is a bipolar disorder in which mood swings and mental disturbances are much less pronounced than in bipolar disorder type I. However, cyclothymia, like dysthymic disorder, can cause severe mental disturbances and disability.

Diagnostic criteria for cyclothymia

• The presence of periods of psychomanic symptoms and periods of depressive symptoms (not meeting the criteria for a major depressive episode), which are repeated many times over a period of at least 2 years. Note: in children and adolescents, the duration of symptoms must be at least 1 year.
• For 2 years (for children and adolescents for 1 year), the above-mentioned symptoms were absent for no more than 2 months in a row.
• During the first 2 years of illness onset, there were no major depressive, manic or mixed episodes.

Note: after the first 2 years (in children and adolescents - after 1 year) of the disease, the occurrence of manic or mixed episodes of discomfort (in this case, bipolar disorder type I and cyclothymia are diagnosed simultaneously) or major depressive episodes (in this case, bipolar disorder type II and cyclothymia are diagnosed simultaneously) is allowed.

• The symptoms listed in the first criterion are not better explained by schizoaffective disorder and do not occur in the setting of schizophrenia, schizophrenia, schizophreniform disorder, delusional disorder, or unspecified psychotic disorder.
• The presenting symptoms are not caused by the direct physiological action of exogenous substances (including addictive substances or drugs) or general diseases (e.g. thyrotoxicosis).

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Comorbid disorders and other factors influencing treatment

The course of the disease, patient compliance and the choice of drugs are significantly influenced by comorbid diseases and a number of other factors.

Substance abuse

According to epidemiological studies, patients with bipolar disorder are more likely to have comorbid substance abuse or dependence than other major mental illnesses. Bipolar disorder is found in 2-4% of patients with alcoholism undergoing treatment under a special program, as well as in 4-30% of patients undergoing treatment for cocaine addiction. As a rule, bipolar disorder and cyclothymia are more common among individuals who abuse psychostimulants than among individuals dependent on opioids and sedatives or hypnotics. On the other hand, 21-58% of hospitalized patients with bipolar disorder are found to have substance abuse. When bipolar disorder and substance abuse are combined, lower compliance and longer hospitalizations are observed; Diagnostic difficulties are also not uncommon, since the abuse of psychostimulants can mimic hypomania or mania, and their withdrawal can mimic many manifestations of depression.

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Other disorders

An epidemiological study showed that 8-13% of patients with bipolar disorder have obsessive-compulsive disorder, 7-16% have panic disorder, and 2-15% have bulimia.

Treating all three of these conditions with antidepressants in patients with bipolar disorder is difficult. When a patient with bipolar disorder has comorbid panic disorder, the use of benzodiazepines is limited by the high risk of developing dependence on psychotropic drugs. Migraine is more common in patients with bipolar disorder than in the general population. On the other hand, one study noted that bipolar disorder is 2.9 times more common among migraine patients than in the general population. Of particular interest in this regard is the fact that valproic acid has been shown to be effective in both conditions.

Secondary mania

Secondary mania is a condition caused by a somatic or neurological disease, the effects of drugs, or substance abuse. Secondary mania usually begins at a later age with no family history. One of the causes of secondary mania may be traumatic brain injury, and it most often occurs with damage to the right subcortical structures (thalamus, "caudate" nucleus) or those areas of the cortex that are closely associated with the limbic system (basal temporal cortex, orbitofrontal cortex).

Cases of secondary mania have been described in multiple sclerosis, hemodialysis, correction of hypocalcemia, hypoxia, tick-borne borreliosis (Lyme disease), polycythemia, cerebrovascular diseases, neurosarcoidosis, tumors, AIDS, neurosyphilis, and in connection with the use of corticosteroids, amphetamines, baclofen, bromides, bromocriptine, captopril, cimetidine, cocaine, cyclosporine, disulfiram, hallucinogens, hydralazine, isoniazid, levodopa, methylphenidate, metrizamide, opioids, procarbazine, procyclidine, yohimbine. The secondary nature of mania may be indicated by: late onset, absence of mental illness in the family history, physiological changes associated with somatic or neurological pathology, recent prescription of a new drug.

Bipolar disorder, not elsewhere classified

Bipolar disorder, not elsewhere classified, refers to disorders with distinct bipolar features that do not meet the criteria for another bipolar disorder.

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