Unipolar Disorder / Major Depression



Diagnostic Criteria for the most common mental disorders including: description, diagnosis, treatment, and research findings. This list references the diagnostic criteria of mental disorders as described in the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV), published by the American Psychiatric Association, Washington D.C., 1994, the main diagnostic reference of Mental Health professionals in the United States of America.



At least one of the following three abnormal moods which significantly interfered with the person's life:

  • Abnormal depressed mood most of the day, nearly every day, for at least 2 weeks.
  • Abnormal loss of all interest and pleasure most of the day, nearly every day, for at least 2 weeks.
  • If 18 or younger, abnormal irritable mood most of the day, nearly every day, for at least 2 weeks.

At least five of the following symptoms have been present during the same 2 week depressed period.

  • Abnormal depressed mood (or irritable mood if a child or adolescent) [as defined in criterion A].
  • Abnormal loss of all interest and pleasure [as defined in criterion A2].
  • Appetite or weight disturbance, either:
    • Abnormal weight loss (when not dieting) or decrease in appetite.
    • Abnormal weight gain or increase in appetite.
  • Sleep disturbance, either abnormal insomnia or abnormal hypersomnia.
  • Activity disturbance, either abnormal agitation or abnormal slowing (observable by others).
  • Abnormal fatigue or loss of energy.
  • Abnormal self-reproach or inappropriate guilt.
  • Abnormal poor concentration or indecisiveness.
  • Abnormal morbid thoughts of death (not just fear of dying) or suicide.

The symptoms are not due to a mood-incongruent psychosis.

There has never been a Manic Episode, a Mixed Episode, or a Hypomanic Episode.

The symptoms are not due to physical illness, alcohol, medication, or street drugs.

The symptoms are not due to normal bereavement.


By definition, Major Depressive Disorder cannot be due to:

  • Physical illness, alcohol, medication, or street drug use.
  • Normal bereavement
  • Bipolar Disorder
  • Mood-incongruent psychosis (e.g., Schizoaffective Disorder, Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified).


Major Depressive Disorder causes the following mood symptoms:

Abnormal depressed mood

Sadness is usually a normal reaction to loss. However, in Major Depressive Disorder, sadness is abnormal because it:

  • Persists continuously for at least 2 weeks.
  • Causes marked functional impairment.
  • Causes disabling physical symptoms (e.g., disturbances in sleep, appetite, weight, energy, and psychomotor activity).
  • Causes disabling psychological symptoms (e.g., apathy, morbid preoccupation with worthlessness, suicidal ideation, or psychotic symptoms).

The sadness in this disorder is often described as a depressed, hopeless, discouraged, "down in the dumps," "blah," or empty. This sadness may be denied at first. Many complain of bodily aches and pains, rather than admitting to their true feelings of sadness.


Abnormal loss of interest and pleasure mood

The loss of interest and pleasure in this disorder is a reduced capacity to experience pleasure which in its most extreme form is called anhedonia.

The resulting lack of motivation can be quite crippling.



Abnormal irritable mood

This disorder may present primarily with irritable, rather than depressed or apathetic mood. This is not officially recognized yet for adults, but it is recognized for children and adolescents.

Unfortunately, irritable depressed individuals often alienate their loved ones with their cranky mood and constant criticisms.



Major Depressive Disorder causes the following physical symptoms:

  • Abnormal appetite: Most depressed patients experience loss of appetite and weight loss. The opposite, excessive eating and weight gain, occurs in a minority of depressed patients. Changes in weight can be significant.


  • Abnormal sleep: Most depressed patients experience difficulty falling asleep, frequent awakenings during the night or very early morning awakening. The opposite, excessive sleeping, occurs in a minority of depressed patients.


  • Fatigue or loss of energy: Profound fatigue and lack of energy usually is very prominent and disabling.


  • Agitation or slowing: Psychomotor retardation (an actual physical slowing of speech, movement and thinking) or psychomotor agitation (observable pacing and physical restlessness) often are present in severe Major Depressive Disorder.



Major Depressive Disorder causes the following cognitive symptoms

  • Abnormal self-reproach or inappropriate guilt

    This disorder usually causes a marked lowering of self-esteem and self-confidence with increased thoughts of pessimism, hopelessness, and helplessness. In the extreme, the person may feel excessively and unreasonably guilty.

    The "negative thinking" caused by depression can become extremely dangerous as it can eventually lead to extremely self-defeating or suicidal behavior.



  • Abnormal poor concentration or indecisiveness

    Poor concentration is often an early symptom of this disorder. The depressed person quickly becomes mentally fatigued when asked to read, study, or solve complicated problems.

    Marked forgetfulness often accompanies this disorder. As it worsens, this memory loss can be easily mistaken for early senility (dementia).



  • Abnormal morbid thoughts of death (not just fear of dying) or suicide

    The symptom most highly correlated with suicidal behavior in depression is hopelessness.




If depressive symptoms are present, determine:

  • Time course and severity
  • Any prior episodes and level of recovery
  • Any history of manic or hypomanic episodes
  • If other major psychiatric disorders are present. Any suicidal ideation, plan, or intent




Evaluate for possible related medical conditions: anemia, hypothyroidism, chronic infection, substance abuse, or medication side effects (oral contraceptives, antihypertensives, etc.).



Lab tests:

Screen for medical causes of depression (if suspected by history or physical examination). Lab tests may include complete blood count with differential, electrolytes, renal and liver functions, thyroid studies, etc.




Indicated if serious suicidal ideation is present (with a plan and access to the means), patient is dangerous to self or others, there is a complicating medical condition, or there is a lack of support system at home.




Most antidepressants believed to be equally effective in equivalent therapeutic doses. Expect a 2- to 6- week latent period before the full effect is seen at therapeutic doses.

To prevent relapse, continue medication for at least 4 to 9 months after patient becomes asymptomatic. For recurrent depression, consider chronic prophylactic therapy.



Tricyclic Antidepressants (TCAs):

A rational method for selecting a TCA is to narrow the choice to a dimethylated TCA (such as imipramine) and a monomethylated TCA (such as nortriptyline). Choose between them based on patient's sedation requirements and ability to tolerate orthostatic hypotension, weight gain, and anticholinergic adverse effects. TCAs are usually given QHS to take advantage of sedating effects. All TCAs may cause slowing of cardiac conduction. May be fatal in overdoses around 2000 mg or more in adults. A therapeutic trial usually is considered >100 mg/day of amitriptyline or its equivalent for at least 3 weeks. Note: Nortriptyline (Pamelor) has a "therapeutic window" plasma level of 50 to 150 ng/ml for optimal efficacy. It has the lowest risk for orthostatic hypotension of all TCAs making it a safe choice in the geriatric patient.



Second-generation Antidepressants:

Selective Serotonin Reuptake Inhibitors (SSRIs):
Much safer in overdose than TCAs. Expensive in contrast to generic TCAs. Initial dose often an effective dose. May need to start at lower doses in the elderly or others sensitive to side effects. Side effects vary and may include nausea, anorexia, insomnia or mild sedation, sweating, headache, tremor, sexual dysfunction, and nervousness. Fluoxetine (Prozac) may have a slower onset of action than other SSRIs. Safety in patients with cardiovascular disease not well studied. Fluvoxamine (Luvox) is contraindicated with astemizole and terfenadine. All SSRIs contraindicated with MAOIs. If switching from a SSRI to a MAOI, need a drug-free period of 14 days for paroxetine (Paxil), sertraline (Zoloft) or fluvoxamine (Luvox) or 5 weeks for fluoxetine (Prozac) .

Bupropion (Wellbutrin):
Safer in overdose than TCAs. Safer choice in patients with history of cardiac disease. Very low incidence of sexual dysfunction compared to SSRIs, TCAs, and MAOIs. TID schedule and 150 mg maximum single dose to minimize the risk of seizures (0.4%). Contraindicated in patients with seizure disorder, bulimia, or anorexia nervosa.

Venlafaxine (Effexor):
Monitor for blood pressure elevation.

Trazodone (Desyrel):
Patients with cardiac disease should be closely monitored. Used as monotherapy or adjunct to certain antidepressants for sedation at bedtime. Risk of priapism 1:6000.

Nefazodone (Serzone):
A newer treatment option for patients experiencing either poor response or intolerable side effects from other antidepressants. Contraindicated with astemizole and terfenadine.

Mirtazapine (Remeron):
A newer option for patients with a poor response or an inability to tolerate other antidepressants.



Monoamine Oxidase Inhibitors (MAOIs):

Sometimes used in depression refractory to the other treatments. Consider consulting psychiatrist before starting because of the serious adverse effect potential.




Supportive therapy is always part of depression treatment. Other types of psychotherapy may be helpful in mild to moderate depression, alone or with medication.



Electroconvulsive Therapy:

Highly controversial treatment and the jury is still out. No explanation or theory for its sometimes surprising efficacy has yet been produced. However, ECT is sometimes the most effective, rapid method of treating severe major depressive disorder (MDD). Indicated for patients with poor response to medications, poor tolerance of usual antidepressants, severe vegetative symptoms, or psychotic features. The decision to administer ECT should be made by a psychiatrist.




80 to 90% of individuals with Major Depressive Disorder also have anxiety symptoms (e.g., anxiety, obsessive preoccupation's, panic attacks, phobias, and excessive health concerns). Separation Anxiety may be prominent in children.

About one third of individuals with Major Depressive Disorder also have a full-blown anxiety disorder (usually either Panic Disorder, Obsessive-Compulsive Disorder, or Social Phobia).

Anxiety in a person with major depression leads to a poorer response to treatment, poorer social and work function, greater likelihood of chronicity and an increased risk of suicidal behavior.



Eating Disorders:

Individuals with Anorexia Nervosa and Bulimia Nervosa often develop Major Depressive Disorder.




Mood congruent delusions or hallucinations may accompany severe Major Depressive Disorder.



Substance Abuse:

The combination of Major Depressive Disorder and substance abuse is common (especially Alcohol and Cocaine).

Alcohol or street drugs are often mistakenly used as a remedy for depression. However, this abuse of alcohol or street drugs actually worsens Major Depressive Disorder.

Depression may also be a consequence of drug or alcohol withdrawal and is commonly seen after cocaine and amphetamine use.



Medical Illness:

25% of individuals with severe, chronic medical illness (e.g., diabetes, myocardial infarction, carcinomas, stroke) develop depression.

About 5% of individuals initially diagnosed as having Major Depressive Disorder subsequently are found to have another medical illness which was the cause of their depression.

Medical conditions often causing depression are:

  • Endocrine disorders: hypothyroidism, hyperparathyroidism, Cushing's disease, and diabetes mellitus.
  • Neurological disorders: multiple sclerosis, Parkinson's disease, migraine, various forms of epilepsy, encephalitis, brain tumors.
  • Medications: many medications can cause depression, especially antihypertensive agents such as calcium channel blockers, beta blockers, analgesics and some anti-migraine medications.




Up to 15% of patients with severe Major Depressive Disorder die by suicide. Over age 55, there is a fourfold increase in death rate.



Premorbid History:

10-25% of patients with Major Depressive Disorder have preexisting Dysthymic Disorder. These "double depressions" (i.e., Dysthymia + Major Depressive Disorder) have a poorer prognosis.




Males and females are equally affected by Major Depressive Disorder prior to puberty. After puberty, this disorder is twice as common in females as in males. The highest rates for this disorder are in the 25- to 44-year-old age group.




The lifetime risk for Major Depressive Disorder is 10% to 25% for women and from 5% to 12% for men. At any point in time, 5% to 9% of women and 2% to 3% of men suffer from this disorder. Prevalence is unrelated to ethnicity, education, income, or marital status.




Average age at onset is 25, but this disorder may begin at any age.



Psychological stress:

Stress appears to play a prominent role in triggering the first 1-2 episodes of this disorder, but not in subsequent episodes.




An average episode lasts about 9 months.




Course is variable. Some people have isolated episodes that are separated by many years, whereas others have clusters of episodes, and still others have increasingly frequent episodes as they grow older.

About 20% of individuals with this disorder have a chronic course.




The risk of recurrence is about 70% at 5 year follow up and at least 80% at 8 year follow-up.

After the first episode of Major Depressive Disorder, there is a 50%-60% chance of having a second episode, and a 5-10% chance of having a Manic Episode (i.e., developing Bipolar I Disorder).

After the second episode, there is a 70% chance of having a third.

After the third episode, there a 90% chance of having a fourth.
The greater number of previous episodes is an important risk factor for recurrence.




For patients with severe Major Depressive Disorder, 76% on antidepressant therapy recover, whereas only 18% on placebo recover. For these severely depressed patients, significantly more recover on antidepressant therapy than on interpersonal psychotherapy. For these same patients, cognitive therapy has been shown to be no more effective than placebo.

New research shows that a medication/psychotherapy combination - preferably Cognitive Behavior Therapy - seems to be most effective.



Poor Outcome:

Poor outcome or chronicity in Major Depressive Disorder is associated with the following:

  • Inadequate treatment
  • Severe initial symptoms
  • Early age of onset
  • Greater number of previous episodes
  • Only partial recovery after one year
  • Having another severe mental disorder (e.g. Alcohol Dependency, Cocaine Dependency)
  • Severe chronic medical illness
  • Family dysfunction



Familial Pattern And Genetics:

There is strong evidence that major depression is, in part, a genetic disorder:

Individuals who have parents or siblings with Major Depressive Disorder have a 1.5-3 times higher risk of developing this disorder.

The concordance for major depression in monozygotic twins is substantially higher than it is in dizygotic twins. However, the concordance in monozygotic twins is in the order of about 50%, suggesting that factors other than genetic factors are also involved.

Children adopted away at birth from biological parents who have a depressive illness carry the same high risk as a child not adopted away, even if they are raised in a family where no depressive illness exists.

Interestingly, families having Major Depressive Disorder have an increased risk of developing Alcoholism and Attention Deficit/Hyperactivity Disorder.

Some disorders display similar or sometimes even the same symptoms. The clinician, therefore, in his diagnostic attempt has to differentiate against the following disorders which he needs to rule out to establish a precise diagnosis.



Exclude depressions due to physical illness, medications, or street drug use:

If due to physical illness, diagnose: Mood Disorder Due to a General Medical Condition.

If due to alcohol, diagnose: Alcohol-Induced Mood Disorder.

If due to other substance use, diagnose: Other Substance-Induced Mood Disorder.



Organic Causes Of Severe Depression:

Illnesses: Organic Mood Syndromes caused by: Acquired Immune Deficiency Syndrome (AIDS), Adrenal (Cushing's or Addison's Diseases), Cancer (especially pancreatic and other GI), Cardiopulmonary disease, Dementias (including Alzheimer's Disease); Epilepsy, Fahr's Syndrome, Huntington's Disease, Hydrocephalus, Hyperaldosteronism, Infections (including HIV and neurosyphilis), Migraines, Mononucleosis, Multiple Sclerosis, Narcolepsy, Neoplasms, Parathyroid Disorders (hyper- and hypo-), Parkinson's Disease, Pneumonia (viral and bacterial), Porphyria, Postpartum, Premenstrual Syndrome, Progressive Supranuclear Palsy, Rheumatoid Arthritis, Sjogren's Arteritis, Sleep Apnea, Stroke, Systemic Lupus Erythematosus, Temporal Arteritis, Trauma, Thyroid Disorders (hypothyroid and "apathetic" hyperthyroidism), Tuberculosis, Uremia (and other renal diseases), Vitamin Deficiencies (B12, C, folate, niacin, thiamine), Wilson's Disease.

Drugs: Acetazolamine, Alphamethyldopa, Amantadine, Amphetamines, Ampicillin, Azathioprine (AZT), 6-Azauridine, Baclofen, Beta Blockers, Bethanidine, Bleomycin, Bromocriptine, C-Asparaginase, Carbamazepine, Choline, Cimetidine, Clonidine, Clycloserin, Cocaine, Corticosteroids (including ACTH), Cyproheptadine, Danazol, Digitalis, Diphenoxylate, Disulfiram, Ethionamide, Fenfluramine, Griseofulvin, Guanethidine, Hydralazine, Ibuprofen, Indomethacin, Lidocaine, Levodopa, Methoserpidine, Methysergide, Metronidazole, Nalidixic Acid, Neuroleptics (butyrophenones, phenothiazines, oxyindoles), Nitrofurantoin, Opiates, Oral Contraceptives, Phenacetin, Phenytoin, Prazosin, Prednisone, Procainamide, Procyclidine, Quanabenzacetate, Rescinnamine, Reserpine, Sedative/Hypnotics (barbiturates, benzodiazepines, chloral hydrate), Streptomycin, Sulfamethoxazole, Sulfonamides, Tetrabenazine, Tetracycline, Triamcinolone, Trimethoprim, Veratrum, Vincristine.



Exclude depressions having a previous history of elevated, expansive, or euphoric mood:

If previous history of a Manic Episode, diagnose: Bipolar I Disorder.

If previous history of recurrent Major Depressive Episodes and at least one Hypomanic Episode, diagnose: Bipolar II Disorder.

If previous history of recurrent Hypomanic Episodes and brief, mild depressive episodes (milder than Major Depressive Episodes), diagnose: Cyclothymic Disorder.



Exclude depressions that merely represent normal bereavement, instead diagnose:

Uncomplicated Bereavement.



Exclude depressions associated with mood-incongruent psychosis:

If previous history of at least 2 weeks of delusions or hallucinations occurring in the absence of prominent mood symptoms, diagnose either: Schizoaffective Disorder, Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified.



Exclude mild depressions:

If only mild depression present for most of past 2 years (or 1 year in children), diagnose: Dysthymic Disorder.

If only brief mild depression clearly triggered by stress, diagnose: Adjustment Disorder with Depressed Mood, or Adjustment Disorder with Mixed Anxiety and Depressed Mood.

If mild depression is clinically significant, but does not meet the criteria for any of the previously described disorders, diagnose: Depressive Disorder Not Otherwise Specified.

In the elderly, it is often difficult to distinguish between early dementia or Major Depressive Disorder:

  • If there is a premorbid history of declining cognitive function in the absence of severe depression, diagnose: Dementia.
  • If there was a relatively normal premorbid state and somewhat abrupt cognitive decline associated with severe depression, diagnose: Major Depressive Disorder.