Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown but probably involves heredity, changes in neurotransmitter levels, altered neuroendocrine function, and psychosocial factors. Diagnosis is based on history. Treatment usually consists of drugs, psychotherapy, or both and sometimes electroconvulsive therapy.

The term depression is often used to refer to any of several depressive disorders. Three are classified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR) by specific symptoms:

Major depressive disorder (often called major depression)

Dysthymia

Depressive disorder not otherwise specified

Two others are classified by etiology:

Depressive disorder due to a general physical condition

Substance-induced depressive disorder

Depressive disorders occur at any age but typically develop during the mid teens, 20s, or 30s. In primary care settings, as many as 30% of patients report depressive symptoms, but < 10% have major depression.

The term depression is often used to describe the low or discouraged mood that results from disappointments or losses. However, a better term for such a mood is demoralization. The negative feelings of demoralization, unlike those of depression, resolve when circumstances or events improve; the low mood usually lasts days rather than weeks or months, and suicidal thoughts and prolonged loss of function are much less likely.

Etiology

Exact cause is unknown, but genetic and environmental factors contribute.

Heredity accounts for about half of the etiology (less so in late-onset depression). Thus, depression is more common among 1st-degree relatives of depressed patients, and concordance between identical twins is high. Also, genetic factors probably influence the development of depressive responses to adverse events.

Other theories focus on changes in neurotransmitter levels, including abnormal regulation of cholinergic, catecholaminergic (noradrenergic or dopaminergic), and serotonergic (5-hydroxytryptamine) neurotransmission. Neuroendocrine dysregulation may be a factor, with particular emphasis on 3 axes: hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, and growth hormone.

Psychosocial factors also seem to be involved. Major life stresses, especially separations and losses, commonly precede episodes of major depression; however, such events do not usually cause lasting, severe depression except in people predisposed to a mood disorder.

People who have had an episode of major depression are at higher risk of subsequent episodes. People who are introverted and who have anxious tendencies may be more likely to develop a depressive disorder. Such people often do not develop the social skills to adjust to life pressures. Depression may also develop in people with other mental disorders.

Women are at higher risk, but no theory explains why. Possible factors include greater exposure to or heightened response to daily stresses, higher levels of monoamine oxidase (the enzyme that degrades neurotransmitters considered important for mood), higher rates of thyroid dysfunction, and endocrine changes that occur with menstruation and at menopause. In postpartum depression (see Postpartum Care and Associated Disorders: Postpartum Depression), symptoms develop within 4 wk after delivery; endocrine changes have been implicated, but the specific cause is unknown.

In seasonal affective disorder, symptoms develop in a seasonal pattern, typically during autumn or winter; the disorder tends to occur in climates with long or severe winters.

Depressive symptoms or disorders may accompany various physical disorders, including thyroid and adrenal gland disorders, benign and malignant brain tumors, stroke, AIDS, Parkinson's disease, and multiple sclerosis (see Table 1: Mood Disorders: Some Causes of Symptoms in Depression and Mania). Certain drugs, such as corticosteroids, some &#946;-blockers, interferon, and reserpine

, can also result in depressive disorders. Abuse of some
recreational drugs (eg, alcohol, amphetamines) can lead to or accompany depression. Toxic effects or withdrawal of drugs may cause transient depressive symptoms.

Table 1

Some Causes of Symptoms in Depression and Mania

Type of Disorder
Depression
Mania

Connective tissue
SLE
Rheumatic fever

SLE

Endocrine
Addison's disease

Cushing's disease

Diabetes mellitus

Hyperparathyroidism

Hyperthyroidism

Hypothyroidism

Hypopituitarism

Hypogonadism
Hyperthyroidism

Infectious
AIDS

General paresis (parenchymatous neurosyphilis)

Influenza

Infectious mononucleosis

TB

Viral hepatitis

Viral pneumonia
AIDS

General paresis

Influenza

St. Louis encephalitis

Neoplastic
Cancer of the head of the pancreas

Disseminated carcinomatosis


Neurologic
Cerebral tumors

Complex partial seizures (temporal lobe)

Head trauma

Multiple sclerosis

Parkinson's disease

Sleep apnea

Stroke (left frontal)
Complex partial seizures (temporal lobe)

Diencephalic tumors

Head trauma

Huntington's disease

Multiple sclerosis

Stroke

Nutritional
Pellagra

Pernicious anemia


Other*
Coronary artery disease

Fibromyalgia

Renal or hepatic failure


Pharmacologic
Amphetamine withdrawal

Amphotericin B






Anticholinesterase insecticides

Barbiturates

&#946;-Blockers (some, eg, propranolol

)

Cimetidine



Corticosteroids

Cycloserine



Estrogen therapy

Indomethacin



Interferon

Mercury

Methyldopa



Metoclopramide



Oral contraceptives

Phenothiazines

Reserpine



Thallium

Vinblastine



Vincristine


Amphetamines

Certain antidepressants

Bromocriptine



Cocaine

Corticosteroids

Levodopa

Methylphenidate




Sympathomimetic drugs

Mental
Alcoholism and other substance use disorders

Antisocial personality

Anxiety disorders

Dementing disorders in the early phase

Schizophrenic disorders


*Depression commonly occurs in these disorders, but no causal relationship has been established.



Symptoms and Signs

Depression causes cognitive, psychomotor, and other types of dysfunction (eg, poor concentration, fatigue, loss of sexual desire, loss of pleasure), as well as a depressed mood. Other mental symptoms or disorders (eg, anxiety and panic attacks) commonly coexist, sometimes complicating diagnosis and treatment.

Patients with all forms of depression are more likely to abuse alcohol or other recreational drugs in an attempt to self-treat sleep disturbances or anxiety symptoms; however, depression is a less common cause of alcoholism and drug abuse than was once thought. Patients are also more likely to become heavy smokers and to neglect their health, increasing the risk of development or progression of other disorders (eg, COPD).

Depression may reduce protective immune responses. Depression increases risk of cardiovascular disorders, MIs, and stroke, perhaps because in depression, cytokines and factors that increase blood clotting are elevated and heart rate variability is decreased�all potential risk factors for cardiovascular disorders.

Major depression (unipolar disorder): Periods (episodes) that include &#8805; 5 mental or physical symptoms and last &#8805; 2 wk are classified as major depression. One of the symptoms must be sadness deep enough to be described as despondency or despair (often called depressed mood) or loss of interest or pleasure in usual activities (anhedonia). Other mental symptoms include feelings of worthlessness or guilt, recurrent thoughts of death or suicide, and a reduced ability to concentrate. Physical symptoms include changes in weight or appetite, loss of energy, fatigue, psychomotor retardation or agitation, and sleep disorders (eg, insomnia, hypersomnia, early morning awakening). Patients may appear miserable, with tearful eyes, furrowed brows, down-turned corners of the mouth, slumped posture, poor eye contact, lack of facial expression, little body movement, and speech changes (eg, soft voice, lack of prosody, use of monosyllabic words). Appearance may be confused with Parkinson's disease. In some patients, depressed mood is so deep that tears dry up; they report that they are unable to experience usual emotions and feel that the world has become colorless and lifeless. Nutrition may be severely impaired, requiring immediate intervention. Some depressed patients neglect personal hygiene or even their children, other loved ones, or pets.

Major depression is often divided into subgroups:

Psychotic: This subgroup is characterized by delusions, often of having committed unpardonable sins or crimes, of harboring incurable or shameful disorders, or of being persecuted. Patients with delusions may also have auditory or visual hallucinations (eg, hearing accusatory or condemning voices). If only voices are described, careful consideration should be given to whether the voices represent true hallucinations.

Catatonic: This subgroup is characterized by severe psychomotor retardation or excessive purposeless activity, withdrawal, and, in some patients, grimacing and mimicry of speech (echolalia) or movement (echopraxia).

Melancholic: This subgroup is characterized by loss of pleasure in nearly all activities, inability to respond to pleasurable stimuli, unchanging emotional expression, excessive or inappropriate guilt, early morning awakening, marked psychomotor retardation or agitation, and significant anorexia or weight loss.

Atypical: This subgroup is characterized by a brightened mood in response to positive events and rejection sensitivity, resulting in depressed overreaction to perceived criticism or rejection, feelings of leaden paralysis or anergy, weight gain or increased appetite, and hypersomnia. Symptoms tend to worsen as the day passes.

Dysthymia: Low-level or subthreshold depressive symptoms that persist for &#8805; 2 yr are classified as dysthymia. Symptoms typically begin insidiously during adolescence and follow a low-grade course over many years or decades (diagnosis requires a course of &#8805; 2 yr); dysthymia may intermittently be complicated by episodes of major depression. Affected patients are habitually gloomy, pessimistic, humorless, passive, lethargic, introverted, hypercritical of self and others, and complaining. Patients with chronic depressive states, whether dysthymia or chronic major depression, are also more likely to have underlying anxiety, substance use, or personality (ie, borderline personality) disorders.

Depression not otherwise specified (NOS): Clusters of symptoms that do not meet criteria for other depressive disorders are classified as depression NOS. For example, minor depressive disorder may involve &#8805; 2 wk of any of the symptoms of major depression but fewer symptoms than the 5 required for diagnosing major depression. Brief depressive disorder involves the same symptoms required for diagnosing major depression but lasts only 2 days to 2 wk. Premenstrual dysphoric disorder involves a depressed mood, anxiety, and decreased interest in activities but only during most menstrual cycles, beginning in the luteal phase and ending within a few days after onset of menses.

Mixed anxiety-depression: Although not considered a type of depression in DSM-IV-TR, this condition, also called anxious depression, refers to concurrent mild symptoms common to anxiety and depression. The course is usually chronically intermittent. Because depressive disorders are more serious, patients with mixed anxiety-depression should be treated for depression.

Diagnosis

Clinical criteria (DSM-IV-TR)

CBC, thyroid-stimulating hormone, vitamin B12, and folate levels to rule out physical disorders that can cause depression

Diagnosis is based on identifying the symptoms and signs (see above). Several brief questionnaires are available for screening. They help elicit some depressive symptoms but cannot be used alone for diagnosis. Specific close-ended questions help determine whether patients have symptoms required by DSM-IV-TR criteria for diagnosis of major depression.

Severity is determined by the degree of pain and disability (physical, social, occupational) and by duration of symptoms. A physician should gently but directly ask patients about any thoughts and plans to harm themselves or others (see Suicidal Behavior). Psychosis and catatonia indicate severe depression. Melancholic features indicate severe or moderate depression. Coexisting physical conditions, substance abuse disorders, and anxiety disorders may add to severity.

Differential diagnosis: Depressive disorders must be distinguished from demoralization. Other mental disorders (eg, anxiety disorders) can mimic or obscure the diagnosis of depression. Sometimes more than one disorder is present. Major depression (unipolar disorder) must be distinguished from bipolar disorder (see Mood Disorders: Bipolar Disorders).

In elderly patients, depression can manifest as dementia of depression (formerly called pseudodementia), which causes many of the symptoms and signs of dementia such as psychomotor retardation and decreased concentration (see Delirium and Dementia: Dementia). However, early dementia may cause depression. In general, when the diagnosis is uncertain, treatment of a depressive disorder should be tried.

Differentiating chronic depressive disorders, such as dysthymia, from substance abuse disorders may be difficult, particularly because they can coexist and may contribute to each other.

Physical disorders must also be excluded as a cause of depressive symptoms. Hypothyroidism often causes symptoms of depression and is common, particularly among the elderly. Parkinson's disease, in particular, may manifest with symptoms that mimic depression (eg, loss of energy, lack of expression, paucity of movement). A thorough neurologic examination is needed to exclude this disorder.

Testing: No laboratory findings are pathognomonic for depressive disorders. Tests for limbic-diencephalic dysfunction are rarely indicated or helpful. However, laboratory testing is necessary to exclude physical conditions that can cause depression. Tests include CBC, TSH levels, and routine electrolyte, vitamin B12, and folate levels. Testing for illicit drug use is sometimes appropriate.

Treatment

Support

Psychotherapy

Drugs

Symptoms may remit spontaneously, particularly when they are mild or of short duration. Mild depression may be treated with general support and psychotherapy. Moderate to severe depression is treated with drugs, psychotherapy, or both and sometimes electroconvulsive therapy. Some patients require a combination of drugs. Improvement may not be apparent until after 1 to 4 wk of drug treatment.

Depression, especially in patients who have had > 1 episode, is likely to recur; therefore, severe cases often warrant long-term maintenance drug therapy. (See also the American Psychiatric Association's Guideline Watch: Practice Guideline for the Treatment of Patients With Major Depressive Disorder, 3rd Edition.)

Most people with depression are treated as outpatients. Patients with significant suicidal ideation, particularly when family support is lacking, require hospitalization, as do those with psychotic symptoms or physical debilitation.

Depressive symptoms in patients with substance abuse disorders often resolve within a few months of stopping substance use. Antidepressant treatment is much less likely to be effective while substance abuse continues.

If a physical disorder or drug toxicity could be the cause, treatment is directed first at the underlying disorder. However, if the diagnosis is in doubt or if symptoms are disabling or include suicidal ideation or hopelessness, a therapeutic trial with an antidepressant or a mood-stabilizing drug may help.

Initial support: Until definite improvement begins, a physician should see patients weekly or biweekly to provide support and education and to monitor progress. Telephone calls may supplement office visits.

Patients and loved ones may be worried or embarrassed about the idea of having a mental disorder. The physician can help by explaining that depression is a serious medical disorder caused by biologic disturbances and requires specific treatment and that the prognosis with treatment is good. Patients and loved ones should be reassured that depression does not reflect a character flaw (eg, laziness, weakness). Telling patients that the path to recovery often fluctuates helps them put feelings of hopelessness in perspective and improves adherence.

Encouraging patients to gradually increase simple activities (eg, taking walks, exercising regularly) and social interactions must be balanced with acknowledging their desire to avoid activities. The physician can suggest that patients avoid self-blame and explain that dark thoughts are part of the disorder and will go away.

Psychotherapy: Psychotherapy, often as cognitive-behavioral therapy (individual or group), alone is often effective for milder forms of depression. Cognitive-behavioral therapy is increasingly used to combat the inertia and self-defeating mental set of depressed patients. However, cognitive-behavioral therapy is most useful when combined with antidepressants to treat moderate to severe depression. Cognitive-behavioral therapy may improve coping skills and enhance gains by providing support and guidance, by removing cognitive distortions that prevent adaptive action, and by encouraging patients to gradually resume social and occupational roles. Couple therapy may help reduce conjugal tensions and disharmony. Long-term psychotherapy is usually unnecessary except for patients who have long-term interpersonal conflicts or who are unresponsive to brief therapy.

Selective serotonin reuptake inhibitors (SSRIs): These drugs prevent reuptake of serotonin (5-hydroxytryptamine [5-HT]). SSRIs include citalopram

, escitalopram


, fluoxetine



,
fluvoxamine

, paroxetine


, and sertraline


. Although these drugs have the same
mechanism of action, differences in their clinical properties make selection important. SSRIs have a wide therapeutic margin; they are relatively easy to administer, with little need for dose adjustment (except for fluvoxamine

).

By preventing reuptake of 5-HT presynaptically, SSRIs result in more 5-HT to stimulate postsynaptic 5-HT receptors. SSRIs are selective to the 5-HT system but not specific for the different 5-HT receptors. They stimulate 5-HT1 receptors, with antidepressant and anxiolytic effects, but they also stimulate 5-HT2 receptors, commonly causing anxiety, insomnia, and sexual dysfunction, and 5-HT3 receptors, commonly causing nausea and headache. Thus, SSRIs can paradoxically relieve and cause anxiety.

A few patients may seem more agitated, depressed, and anxious within a week of starting SSRIs or increasing the dose. Patients and their loved ones should be warned of this possibility and instructed to call the physician if symptoms worsen with treatment. This situation should be closely monitored because some patients, especially younger children and adolescents, become increasingly suicidal if agitation, increased depression, and anxiety are not detected and rapidly treated. Recent studies have determined that children, adolescents, and young adults have an increased rate of suicidal ideation, suicide gestures, and suicide attempts during the first few months of taking SSRIs (the same concern may apply to serotonin modulators, serotonin-norepinephrine

reuptake inhibitors, and
norepinephrine

-dopamine


reuptake inhibitors); physicians must balance this risk with
clinical need.

Sexual dysfunction (especially difficulty achieving orgasm but also decreased libido and erectile dysfunction) occurs in one third or more of patients. Some SSRIs cause weight gain. Others, especially fluoxetine


, may cause anorexia in the first few months. SSRIs have few
anticholinergic, adrenolytic, and cardiac conduction effects. Sedation is minimal or nonexistent, but in the early weeks of treatment, some patients tend to be sleepy during the day. Loose stools or diarrhea occurs in some patients.

Drug interactions are relatively uncommon; however, fluoxetine


, paroxetine


, and
fluvoxamine

can inhibit cytochrome P-450 (CYP450) isoenzymes, which can lead to serious
drug interactions. For example, these drugs can inhibit the metabolism of certain &#946;-blockers, including propranolol

and metoprolol



, potentially resulting in hypotension and bradycardia.
Discontinuation symptoms (eg, irritability, anxiety, nausea) can occur if the drug is stopped abruptly; such effects are less likely with fluoxetine


.

Serotonin modulators (5-HT2 blockers): These drugs block primarily the 5-HT2 receptor and inhibit reuptake of 5-HT and norepinephrine

. Serotonin modulators include nefazodone


,
trazodone

, and mirtazapine


. Serotonin modulators have antidepressant and anxiolytic
effects but do not cause sexual dysfunction. Unlike most antidepressants, nefazodone


does not suppress REM (rapid eye movement) sleep and produces restful sleep. Nefazodone

can significantly interfere with drug-metabolizing liver enzymes and has been
associated with liver failure.

Trazodone

is related to nefazodone


but does not inhibit 5-HT reuptake presynaptically.
Unlike nefazodone

, trazodone


has caused priapism (in 1/1000) and, as an &#945;1-
noradrenergic blocker, may cause orthostatic (postural) hypotension. It is very sedating, so its use in antidepressant doses (> 200 mg/day) is limited. It is most often given in 50- to 100-mg doses at bedtime to depressed patients with insomnia.

Mirtazapine

inhibits 5-HT reuptake and blocks &#945;2-adrenergic autoreceptors, as well as 5-
HT2 and 5-HT3 receptors. The result is increased serotonergic function and increased noradrenergic function without sexual dysfunction or nausea. It has no cardiac adverse effects, has minimal interaction with drug-metabolizing liver enzymes, and is generally well tolerated, although it does cause sedation and weight gain, mediated by H1 (histamine) blockade.

Serotonin-norepinephrine reuptake inhibitors: These drugs (eg, venlafaxine

,
duloxetine

) have a dual 5-HT and norepinephrine


mechanism of action, as do tricyclic
antidepressants. However, their toxicity approximates that of SSRIs. Nausea is the most common problem during the first 2 wk; modest dose-dependent increases in BP occur with high doses. Discontinuation symptoms (eg, irritability, anxiety, nausea) often occur if the drug is stopped suddenly. Duloxetine

resembles venlafaxine


in effectiveness and adverse
effects.

Norepinephrine-dopamine reuptake inhibitors: By mechanisms not clearly understood, these drugs favorably influence catecholaminergic, dopaminergic, and noradrenergic function. They do not affect the 5-HT system.

Bupropion


is currently the only drug in this class. It can help depressed patients with
concurrent attention-deficit/hyperactivity disorder or cocaine dependence and those trying to stop smoking. Bupropion


causes hypertension in a very few patients but has no other
effects on the cardiovascular system. Bupropion


can cause seizures in 0.4% of patients
taking doses > 150 mg tid (or > 200 mg sustained-release [SR] bid or > 450 mg extended-release [XR] once/day); risk is increased in patients with bulimia. Bupropion


does not have
sexual adverse effects and interacts little with coadministered drugs, although it does inhibit the CYP2D6 hepatic enzyme. Agitation, which is common, is considerably attenuated by using the SR or XR form.

Heterocyclic antidepressants: This group of drugs, once the mainstay of treatment, includes tricyclic (tertiary amines amitriptyline


and imipramine


and their secondary amine
metabolites nortriptyline

and desipramine


), modified tricyclic, and tetracyclic
antidepressants. Acutely, these drugs increase the availability of primarily norepinephrine


and, to some extent, 5-HT by blocking reuptake in the synaptic cleft. Long-term use downregulates &#945;1-adrenergic receptors on the postsynaptic membrane�a possible final common pathway of their antidepressant activity.

Although effective, these drugs are now rarely used because overdose causes toxicity and they have more adverse effects than other antidepressants. The more common adverse effects of heterocyclics are due to their muscarinic-blocking, histamine-blocking, and &#945;1-adrenolytic actions. Many heterocyclics have strong anticholinergic properties and are thus unsuitable for the elderly and for patients with benign prostatic hypertrophy, glaucoma, or chronic constipation. All heterocyclics, particularly maprotiline

and clomipramine


, lower the
threshold for seizures.

Monoamine oxidase inhibitors (MAOIs): These drugs inhibit the oxidative deamination of the 3 classes of biogenic amines (norepinephrine

, dopamine


, 5-HT) and other
phenylethylamines. MAOIs have little or no effect on normal mood. Their primary value is for treating refractory or atypical depression when SSRIs, tricyclic antidepressants, and sometimes even electroconvulsive therapy is ineffective.

MAOIs marketed as antidepressants in the US (eg, phenelzine

, tranylcypromine


,
isocarboxazid

) are irreversible and nonselective (inhibiting MAO-A and MAO-B). Another
MAOI (selegiline

), which inhibits only MAO-B at lower doses, is available as a patch.

MAOIs that inhibit MAO-A and MAO-B can cause hypertensive crises if a sympathomimetic drug or food containing tyramine or dopamine

is ingested concurrently. This effect is called
the cheese reaction because mature cheese has a high tyramine content. MAOIs are used infrequently because of concern about this reaction. The lower dosage of the selegiline


patch is considered safe to use without specific dietary restrictions, unless the dosage must be higher than starting levels (a 6-mg patch). More selective and reversible MAOIs (eg, moclobemide

, befloxatone), which inhibit MAO-A, are not yet available in the US; they are
relatively free of these interactions. To prevent hypertension and febrile crises, patients taking MAOIs should avoid sympathomimetic drugs (eg, pseudoephedrine


), dextromethorphan




,
reserpine

, and meperidine


as well as malted beers, Chianti wines, sherry, liqueurs, and
overripe or aged foods that contain tyramine or dopamine

(eg, bananas, fava or broad
beans, yeast extracts, canned figs, raisins, yogurt, cheese, sour cream, soy sauce, pickled herring, caviar, liver, extensively tenderized meats). Patients can carry 25-mg tablets of chlorpromazine

and, as soon as signs of such a hypertensive reaction occur, take 1 or 2
tablets as they head to the nearest emergency department.

Common adverse effects include erectile dysfunction (least common with tranylcypromine

),
anxiety, nausea, dizziness, insomnia, pedal edema, and weight gain. MAOIs should not be used with other classes of antidepressants, and at least 2 wk (5 wk with fluoxetine


, which
has a long half-life) should elapse between use of the 2 classes of drugs. MAOIs used with antidepressants that affect the 5-HT system (eg, SSRIs, nefazodone

) may cause
neuroleptic malignant syndrome (malignant hyperthermia, muscle breakdown, renal failure, seizures, and eventual death�see Heat Illness: Neuroleptic Malignant Syndrome). Patients who are taking MAOIs and who also need antiasthmatic or antiallergic drugs, a local anesthetic, or a general anesthetic should be treated by a psychiatrist plus an internist, a dentist, or an anesthesiologist with expertise in neuropsychopharmacology.

Drug choice and administration: Choice of drug may be guided by past response to a specific antidepressant. Otherwise, SSRIs are often the initial drugs of choice. Although the different SSRIs are equally effective for typical cases, certain properties of the drugs make them more or less appropriate for certain patients (see Table 2: Mood Disorders: Antidepressants ).
Table 2


Antidepressants
This table is presented as a PDF and requires the free Adobe PDF reader. Get Adobe Reader



If one SSRI is ineffective, another SSRI can be substituted, but an antidepressant from a different class may be more likely to help. Tranylcypromine

in high doses (20 to 30 mg
po bid) is often effective for depression refractory to sequential trials of other antidepressants; it should be given by a physician experienced in use of MAOIs. Psychologic support of patients and loved ones is particularly important in refractory cases.

Insomnia, a common adverse effect of SSRIs, is treated by reducing the dose or adding a low dose of trazodone

or another sedating antidepressant. Initial nausea and loose stools
usually resolve, but throbbing headaches do not always go away, necessitating a change in drug class. An SSRI should be stopped if it causes agitation. When decreased libido, impotence, or anorgasmia occur during SSRI therapy, dose reduction may help, or a change can be made to another drug class.

SSRIs, which tend to stimulate many depressed patients, should be given in the morning. Giving the entire heterocyclic antidepressant dose at bedtime usually makes sedatives unnecessary, minimizes adverse effects during the day, and improves adherence. MAOIs are usually given in the morning and early afternoon to avoid excessive stimulation.

Therapeutic response with most classes of antidepressants usually occurs in about 2 to 3 wk (sometimes as early as 4 days or as late as 8 wk). For a first episode of mild or moderate depression, the antidepressant should be given for 6 mo, then tapered gradually over 2 mo. If the episode is severe or is a recurrence or if there is suicidal risk, the dose that produces full remission should be continued during maintenance.

For psychotic depression, imipramine

appears to be more effective than monotherapy with
antidepressants from other classes; dosing this drug can be guided by steady-state plasma levels. The addition of an antipsychotic may improve the likelihood of response, but antipsychotic monotherapy appears to be ineffective.

Continued therapy with an antidepressant for 6 to 12 mo (up to 2 yr in patients > 50) is usually needed to prevent relapse. Most antidepressants, especially SSRIs, should be tapered off (by decreasing the dose by about 25%/wk) rather than stopped abruptly; stopping SSRIs abruptly may result in discontinuation syndrome (nausea, chills, muscles aches, dizziness, anxiety, irritability, insomnia, fatigue). The likelihood and severity of withdrawal varies inversely with the half-life of the SSRI.

Medicinal herbs are used by some patients. St. John's wort (see Dietary Supplements: St. John's Wort) may be effective for mild depression, although data are contradictory. St. John's wort may interact with other antidepressants and other drugs. A number of placebo-controlled studies of &#969;-3 supplementation, used as augmentation or as monotherapy, have suggested that eicosapentaenoic acid 1 to 2 g once/day has useful antidepressant effects.

Electroconvulsive therapy (ECT): Severe suicidal depression, depression with agitation or psychomotor retardation, delusional depression, or depression during pregnancy is often treated with ECT if drugs are ineffective. Patients who have stopped eating may need ECT to prevent death. ECT is also effective for psychotic depression. Response to 6 to 10 ECT treatments is usually dramatic and may be lifesaving. Relapse after ECT is common, and drug therapy is often maintained after ECT is stopped.

Phototherapy: Phototherapy is best known for its effects on seasonal depression but can also be effective in other types of depression. Treatment can be provided at home with 2,500 to 10,000 lux at a distance of 30 to 60 cm for 30 to 60 min/day (longer with a less intense light source). In patients who go to sleep late at night and rise late in the morning, phototherapy is most effective in the morning, sometimes supplemented with 5 to 10 min of exposure between 3 pm and 7 pm. For patients who go to sleep and rise early, phototherapy is most effective between 3 pm and 7 pm.

Other therapies: Psychostimulants (eg, dextroamphetamine


, methylphenidate



) are
sometimes used, often with antidepressants; however, they have not been well studied in controlled clinical trials.

Vagus nerve stimulation involves intermittently stimulating the vagus nerve via an implanted pulse generator. It may be useful for depression refractory to other treatments but usually takes 3 to 6 mo to be effective.

Deep brain stimulation and transcranial magnetic stimulation are still under study.

In order to purify our minds we need to consciously choose pure emotions over impure ones, by rising above conditioning.

In cultivating a saumya personality, we need to start working consciously and conscientiously on purification of the mind and emotions. We need to learn to choose purer emotions. How do we determine what are the purer emotions?

Psychologically speaking, if a certain emotion causes pain in our minds and its expression evokes a painful feeling in those who are in relationship with us, these emotions are not pure ones. If an emotion leaves a smile in our or another's mind, then it is a pure emotion. Spiritually speaking, the emotions that are conducive to enlightenment are the pure ones.

It must be remembered that our emotional choices are learnt ones; they are habits we have formed. In the same situation, one has access to multiple emotional choices. A brave man sees a tiger in the wild and his hunting instinct is activated. A coward sweats with fear and flees. A yogi stays neutral or is filled with non-violent, loving feelings for his fellow living being.

The reaction we choose is from the habits created by our culture, education or personal circumstances.

Here is an example from world cultures. Let us take anger. In certain schools of modern psychology, a therapist works on bringing to the fore our hidden anger and suggests to the client that he give himself permission to express anger. The question of the ethics of emotions plays no part in this. In India we are often advised to control our anger, but display of anger is still commonplace. In the cultures of SE Asia, anger is particularly frowned upon. You arrive after a long flight to a hotel where you had made a reservation and even reconfirmed it, only to be told by the receptionist that you have not made a booking. If, in your state of exhaustion and frustration you display anger, you will be completely ignored. No one will talk to you till you calm yourself down and become civil and gentle.

These are examples of culturally and educationally generated emotional habits. But at a certain time in our lives we begin to examine ourselves. We can make conscious choices, which may be different from those of general culture or family patterns.

or example, boys often see their fathers abusing their mother. As a child the boy's sympathy is with the mother. But as he grows to manhood, he identifies more and more with the father and emulates him.

But one may choose to take a different path internally. One may dig deep and bring to the conscious mind, the unconscious memory of how painful it was, as a young child, to watch his mother being hurt; here one taps the 'son'-personality rather than the 'domineering, insensitive and cruel male' personality.

In USA and other western countries where jurisprudence increasingly takes into account the principles of psychology, it is common for the attorneys to argue that a certain person has abused and hurt his child helplessly because he was conditioned to do so through his own psychological trauma when abused and hurt as a child. The spiritual argument, however, would be based on an extension, a deepening, of the principle of free will. One is free to make one's choice if one is spiritually awake, to go beyond this psychological conditioning.

One may thus make a conscious choice. One may make a resolve to cultivate within oneself the emotional states that create a saumya personality, generating a non-painful feeling and evoking the same in the person(s) in our relationship and opting for that which leads to enlightenment.

Even if we ignore this last goal, the other three are worth pursuing in our quest for purification of emotions, bhava-sam-shuddhi.

Thus we need to begin to look at our emotions not as something that renders us helpless, whose 'accidental' presence we have no choice over, but rather as acts of volition and we choose them on the basis of some moral principles. There you have an ethics of emotions.

As one grows spiritually, one frees oneself more and more from psychological, educational and cultural conditioning. One no longer acts adversely towards women because 'everybody does so'. One does not cast aspersions at people of other ethnic, religious or caste groups just because one is conditioned to believe that he is the best, the highest and the noblest. Spirituality supersedes psychology.

As we have shown, we then choose the noble emotions. We change our past habits and learn to react differently. Part of our spiritual journey consists of emotional de-conditioning of the ignoble and re-conditioning towards the noble. Spiritual guides have employed many internal tools to accomplish this purpose.

Here is just a short explanation of the concept of the ethics of emotions. All through the history of philosophy, sages and philosophers have spoken of three levels of actions: mental, vocal and physical, from manas, vak and kaya, respectively.

In the Zoroastrian tradition we are taught the same: manashni, gavashni, kunashni - to think, to speak and to act in a noble and peace-generating way.

Mental acts are expressed in speech and physical actions. A majority of our mental acts are emotional ones, based not on logic but on feelings and conditioning. This is where the ethics of emotions begins, to discern between right and wrong mental acts and thereby heal your own mind

Schizophrenia is a mental disorder characterized by loss of contact with reality (psychosis), hallucinations (usually, hearing voices), firmly held false beliefs (delusions), abnormal thinking, a restricted range of emotions (flattened affect), diminished motivation, and disturbed work and social functioning.

Schizophrenia is probably caused by hereditary and environmental factors.

People may have a variety of symptoms, ranging from bizarre behavior and rambling, disorganized speech to loss of emotions and little or no speech to inability to concentrate and remember.

Doctors diagnose schizophrenia based on symptoms after they do tests to rule out other possible causes.

How well people do depends largely on whether they take the prescribed drugs as directed.

Treatment involves antipsychotic drugs, rehabilitation and community support activities, and psychotherapy.

Schizophrenia is a major health problem throughout the world. The disorder typically strikes young people at the very time they are establishing their independence and can result in lifelong disability and stigma. In terms of personal and economic costs, schizophrenia has been described as among the worst disorders afflicting humankind.

Schizophrenia is the 9th leading cause of disability worldwide. It affects about 1% of the population. Schizophrenia affects men and women equally. In the United States, schizophrenia accounts for about 1 of every 5 Social Security disability days and 2.5% of all health care expenditures. Schizophrenia is more common than Alzheimer's disease and multiple sclerosis.

Determining when schizophrenia begins (onset) is often difficult because unfamiliarity with symptoms may delay medical care for several years. The average age at onset is 18 for men and 25 for women. Onset during childhood or early adolescence is uncommon (see Mental Health Disorders in Children: Childhood Schizophrenia). Onset is also uncommon late in life.

Deterioration in social functioning can lead to substance abuse, poverty, and homelessness. People with untreated schizophrenia may lose contact with their families and friends and often find themselves living on the streets of large cities.


Did You Know...


Schizophrenia is more common than Alzheimer's disease and multiple sclerosis.

Various disorders, including thyroid disorders, brain tumors, seizure disorders, and other mental health disorders, can cause symptoms similar to those of schizophrenia.



Causes

What precisely causes schizophrenia is not known, but current research suggests a combination of hereditary and environmental factors. Fundamentally, however, it is a biologic problem (involving changes in the brain), not one caused by poor parenting or a mentally unhealthy environment. People who have a parent or sibling with schizophrenia have about a 10% risk of developing the disorder, compared with a 1% risk among the general population. An identical twin whose co-twin has schizophrenia has about a 50% risk of developing schizophrenia. These statistics suggest that heredity is involved.

Other causes may include problems that occurred before, during, or after birth, such as influenza in the mother during the 2nd trimester of pregnancy, oxygen deprivation at birth, a low birth weight, and incompatibility of the mother's and infant's blood type.

Symptoms

The onset of schizophrenia may be sudden, over a period of days or weeks, or slow and insidious, over a period of years. Although the severity and types of symptoms vary among different people with schizophrenia, the symptoms are usually sufficiently severe as to interfere with the ability to work, interact with people, and care for oneself. In some people with schizophrenia, mental function declines, leading to an impaired ability to pay attention, think in the abstract, and solve problems. The severity of mental impairment largely determines overall disability in people with schizophrenia.

Symptoms may be triggered or worsened by environmental stresses, such as stressful life events. Drug use, including use of marijuana, may trigger or worsen symptoms as well.

Categories: Overall, the symptoms of schizophrenia fall into four major categories:

Positive symptoms

Negative symptoms

Disorganization

Cognitive impairment

People may have symptoms from one, two, or all categories.

Positive symptoms involve an excess or a distortion of normal functions. They include the following:

Delusions are false beliefs that usually involve a misinterpretation of perceptions or experiences. For example, people with schizophrenia may have persecutory delusions, believing that they are being tormented, followed, tricked, or spied on. They may have delusions of reference, believing that passages from books, newspapers, or song lyrics are directed specifically at them. They may have delusions of thought withdrawal or thought insertion, believing that others can read their mind, that their thoughts are being transmitted to others, or that thoughts and impulses are being imposed on them by outside forces.

Hallucinations of sound, sight, smell, taste, or touch may occur, although hallucinations of sound (auditory hallucinations) are by far the most common. People may hear voices in their head commenting on their behavior, conversing with one another, or making critical and abusive comments.

Negative symptoms involve a decrease in or loss of normal functions. They include the following:

Blunted affect refers to a flattening of emotions. The face may appear immobile. People make little or no eye contact and lack emotional expressiveness. Events that would normally make them laugh or cry produce no response.

Poverty of speech refers to a decreased amount of speech. Answers to questions may be terse, perhaps one or two words, creating the impression of an inner emptiness.

Anhedonia refers to a diminished capacity to experience pleasure. People may take little interest in previous activities and spend more time in purposeless ones.

Asociality refers to a lack of interest in relationships with other people. These negative symptoms are often associated with a general loss of motivation, sense of purpose, and goals.

Disorganization involves thought disorders and bizarre behavior:

Thought disorder refers to disorganized thinking, which becomes apparent when speech is rambling or shifts from one topic to another. Speech may be mildly disorganized or completely incoherent and incomprehensible.

Bizarre behavior may take the form of childlike silliness, agitation, or inappropriate appearance, hygiene, or conduct. Catatonia is an extreme form of bizarre behavior in which people maintain a rigid posture and resist efforts to be moved or, in contrast, display purposeless and unstimulated motor activity.

Cognitive impairment refers to difficulty concentrating, remembering, organizing, planning, and problem solving. Some people are unable to concentrate sufficiently to read, follow the story line of a movie or television show, or follow directions. Others are unable to ignore distractions or remain focused on a task. Consequently, work that involves attention to detail, involvement in complicated procedures, and decision making may be impossible.










Disorders That Resemble Schizophrenia


General medical and neurologic conditions such as thyroid disorders, brain tumors, seizure disorders, kidney failure, toxic reactions to drugs, and vitamin deficiencies can sometimes cause symptoms similar to those of schizophrenia. In addition, a number of mental disorders share features of schizophrenia.

Brief psychotic disorder: Symptoms of this disorder resemble those of schizophrenia but last only for 1 day to 1 month. This time-limited disorder often occurs in people with a preexisting personality disorder or in people who have experienced a severe stress, such as loss of a loved one.

Schizophreniform disorder: The schizophrenia-like symptoms characteristic of this disorder last for 1 to 6 months. This disorder may resolve or may progress to manic-depressive illness or schizophrenia.

Schizoaffective disorder: This disorder is characterized by the presence of mood symptoms, such as depression or mania, plus more typical symptoms of schizophrenia.

Schizotypal personality disorder: This personality disorder (see Personality Disorders: Schizotypal personality disorder) may share symptoms of schizophrenia, but they are generally not severe enough to meet the criteria for psychosis. People with this disorder tend to be shy and to isolate themselves and may be mildly suspicious and have other disturbances in thinking. Genetic studies indicate that schizotypal personality disorder may be a mild form of schizophrenia.



Subtypes of Schizophrenia: Some researchers believe schizophrenia is a single disorder, but others believe it is a syndrome (a collection of symptoms) based on numerous underlying disorders. Subtypes of schizophrenia have been proposed in an effort to classify people into more distinct groups. However, the subtype in a particular person may change over time. Subtypes include the following:

Paranoid: People are preoccupied with delusions or auditory hallucinations. Disorganized speech and inappropriate emotions are less prominent.

Disorganized: Speech and behavior are disorganized, and people do not express emotions or have inappropriate emotions.

Catatonic: Symptoms are mainly physical. They include immobility, excessive motor activity, and assumption of bizarre postures.

Undifferentiated: People have a mixture of symptoms from the other subtypes: delusions and hallucinations, thought disorder and bizarre behavior, and negative symptoms.

Residual: People have had a clear history of prominent schizophrenia symptoms that are followed by a long period of mild negative symptoms.

Diagnosis

No definitive test exists to diagnose schizophrenia. A doctor makes the diagnosis based on a comprehensive assessment of a person's history and symptoms. Schizophrenia is diagnosed when symptoms persist for at least 6 months and cause significant deterioration in work, school, or social functioning. Information from family members, friends, or teachers is often important in establishing when the disorder began.

Laboratory tests are often done to rule out substance abuse or an underlying medical, neurologic, or hormonal disorder that can have features of psychosis. Examples of such disorders include brain tumors, temporal lobe epilepsy, thyroid disorders, autoimmune disorders, Huntington's disease, liver disorders, and side effects of drugs. Testing for drug abuse is sometimes done.

People with schizophrenia have brain abnormalities that may be seen on a computed tomography (CT) or magnetic resonance imaging (MRI) scan. However, the abnormalities are not specific enough to help in diagnosing schizophrenia.


Did You Know...


About 10% of people with schizophrenia commit suicide.



Prognosis

For people with schizophrenia, the prognosis depends largely on adherence to drug treatment. Without drug treatment, 70 to 80% of people have another episode within the first year after diagnosis. Drugs taken continuously can reduce this percentage to about 20 to 30% and can lessen the severity of symptoms significantly in most people. After discharge from a hospital, people who do not take prescribed drugs are very likely to be readmitted within the year. Taking drugs as directed dramatically reduces the likelihood of being readmitted.

Despite the proven benefit of drug therapy, half of people with schizophrenia do not take their prescribed drugs. Some do not recognize their illness and resist taking drugs. Others stop taking their drugs because of unpleasant side effects. Memory problems, disorganization, or simply a lack of money prevents others from taking their drugs.

Adherence is most likely to improve when specific barriers are addressed. If side effects of drugs are a major problem, a change to a different drug may help. A consistent, trusting relationship with a doctor or other therapist helps some people with schizophrenia to accept their illness more readily and recognize the need for adhering to prescribed treatment.

Over longer periods, the prognosis varies. In general, one third of people achieve significant and lasting improvement, one third achieve some improvement with intermittent relapses and residual disabilities, and one third experience severe and permanent incapacity. Factors associated with a better prognosis include the following:

Sudden onset of the disorder

Older age at onset

A good level of skills and accomplishments before becoming ill

Presence of positive rather than negative symptoms

Factors associated with a poor prognosis include the following:

Younger age at onset

Poor social and vocational functioning before becoming ill

A family history of schizophrenia

Presence of negative rather than positive symptoms

About 10% of people with schizophrenia commit suicide.










What Is Neuroleptic Malignant Syndrome?


Neuroleptic malignant syndrome is unresponsiveness caused by use of certain antipsychotic drugs. It develops in up to 3% of people who are treated with antipsychotic drugs, usually within the first few weeks of treatment. The syndrome is most common among men who, because they are agitated, are given rapidly increased doses of the drugs or high doses initially.

Symptoms include muscle rigidity, a dangerously high temperature, a fast heart rate, a fast breathing rate, high blood pressure, and coma. Damaged muscles release the protein myoglobin, which is excreted in the urine. Myoglobin turns the urine brown. This condition (myoglobinuria) can result in kidney damage or even kidney failure.

People with this syndrome are usually treated in an intensive care unit. The antipsychotic drug is stopped, fever is controlled (usually by wetting people and blowing air on them and by placing special cooling blankets on them). People are also given a muscle relaxant (such as bromocriptine

or dantrolene
). Giving sodium bicarbonate
intravenously helps prevent myoglobulinuria by making the urine alkaline.

Almost 30% of people with this syndrome die, but most of the rest recover completely. After recovery, up to 30% of people develop the syndrome again if they are given the same antipsychotic drug.



Treatment

Generally, treatment aims

To reduce the severity of psychotic symptoms

To prevent the recurrence of symptomatic episodes and the associated deterioration in functioning

To provide support and thus enable people to function at the highest level possible

Antipsychotic drugs, rehabilitation and community support activities, and psychotherapy are the major components of treatment.

Antipsychotic Drugs: Drugs can be effective in reducing or eliminating symptoms, such as delusions, hallucinations, and disorganized thinking. After the immediate symptoms have cleared, the continued use of antipsychotic drugs substantially reduces the probability of future episodes. However, antipsychotic drugs have significant side effects, which can include drowsiness, muscle stiffness, tremors, weight gain, and motor restlessness. Antipsychotic drugs may also cause tardive dyskinesia, an involuntary movement disorder most often characterized by puckering of the lips and tongue or writhing of the arms or legs. Tardive dyskinesia may not go away even after the drug is stopped. For tardive dyskinesia that persists, there is no effective treatment. A rare but potentially fatal side effect of antipsychotic drugs is neuroleptic malignant syndrome. It is characterized by muscle rigidity, fever, high blood pressure, and changes in mental function (such as confusion and lethargy).

Some newer antipsychotic drugs, termed second-generation antipsychotic drugs, have fewer side effects. However, these drugs seem to cause significant weight gain. They also increase the risk of the metabolic syndrome (see Obesity and the Metabolic Syndrome: Metabolic Syndrome). In this syndrome, fat accumulates in the abdomen, blood levels of triglycerides (a fat) are elevated, levels of high density cholesterol (HDL, the �good� cholesterol) are low, and blood pressure is high. Also, insulin is less effective (called insulin resistance), increasing the risk of diabetes. These drugs may relieve positive symptoms (such as hallucinations), negative symptoms (such as lack of emotion), and cognitive impairment (such as reduced mental functioning and attention span) to a greater extent than the older antipsychotic drugs, although some doctors question these differences.

Clozapine
, the first of the second-generation antipsychotic drugs, is effective in up to half of
people who do not respond to other antipsychotic drugs. However, clozapine
can have
serious side effects, such as seizures or potentially fatal suppression of bone marrow activity (which includes making blood cells). Thus, it is usually used only for people who have not responded to other antipsychotic drugs. People who take clozapine
must have their white
blood cell count measured weekly, at least for the first 6 months, so that clozapine
can be
stopped at the first indication that the number of white blood cells is decreasing.

Rehabilitation and Community Support Activities: Community support activities, such as on-the-job coaching, are directed at teaching the skills needed to survive in the community. These skills enable people with schizophrenia to work, shop, care for themselves, manage a household, and get along with others. Hospitalization may be needed during severe relapses, and involuntary hospitalization may be needed if people pose a danger to themselves or others. However, the general goal is to have people live in the community. To achieve this goal, some people need to live in a supervised apartment or group home where someone can ensure that drugs are taken as prescribed.

A few people with schizophrenia are unable to live independently, either because they have severe, persistent symptoms or because they lack the skills necessary to live in the community. They usually require full-time care in a safe and supportive setting.

Psychotherapy: Generally, psychotherapy aims to establish a collaborative relationship between people, their family members, and doctor. That way people may learn to understand and manage their disorder, to take antipsychotic drugs as prescribed, and to manage stresses that can aggravate the disorder. A good doctor-patient relationship is often a major determinant of whether treatment is successful. Psychotherapy reduces the severity of symptoms in some people and helps prevent relapse in others.

ART OF IMMORTALITY: DR. SHRINIWAS KASHALIKAR

Bhagavadgeeta implies; �Our turning towards (in acceptance); the Absolute Truth"; by overcoming the enormous dragging by the MOHA i.e. the relative truth (from inside and outside).

This is exactly implied in NAMASMARAN, which is a constant and continuous reaffirmation of the victory of; Absolute Truth over the relative truth, immortality over mortality and infinite over finite. It is an act of victorious celebration (not at all easy; in face of physical pain, incapacitation, old age, poverty, failures, humiliations and all �appearances� that call for disapproval, disgruntlement or point blank protest).

NAMASMARAN thus involves; the offering of everything; �good and bad� in life and its results (and total surrender) by us; the fallible, weak, humble subjectivity, relative truth (SHISHYA); to the infallible, omniscient, omnipresent and omnipotent objectivity, Absolute Truth (GURU); thus gratefully welcoming the cosmic objective desire to manifest (GURUKRUPA); towards universal benevolence and individual fulfillment.

Bhagavadgeeta upholds SWADHARMA i.e. doing every action by inspired by the Absolute Truth; as is the case in NAMASMARAN, which is therefore a choicest and supreme act of assertion.

KUNDALI, KUNDALINI AND PRARABDHA: DR. SHRINIWAS KASHALIKAR

NAMASMARAN (JAP, JAAP, JIKRA, SUMIRAN, SIMARAN i.e. SELF RECOLLECTION) is an eternal process. Every visionary and incarnation of absolute truth; being omnipresent; emancipates the KUNDALI, KUNDALINI and PRARABDHA of every cell, every individual and the whole universe. This is holistic renaissance or superliving or SAMASHTI YOGA. We are inseparable part of this!

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