Unipolar depressive disorder is a mood disorder state where life experiences of loss, anger, upset, and frustration outweigh a person's ability to effectively cope with daily experiences. It is characterized by one or more major depressions (requiring at least four or more additional symptoms) without mania and lasting at least two weeks (but typically longer). It involves emotional, cognitive, behavioral, and somatic disturbances. Depression is rated in terms of severity (mild, moderate, severe) and is classified by frequency (single episode, recurrent, or chronic [i.e., lasting more than two years]). There are three subtypes.

• Major depressive disorder—one or more major depressions with or without interepisodic recovery
• Dysthymic disorder—chronic (at least two years), low-grade depression without a major depressive episode
• Depression not otherwise specified—PMS; depressions with psychotic, melancholic, catatonic, or atypical features; and depressions that briefly recur or with postpartum or seasonal patterns

Psychodynamic influences (e.g., chronic stress, especially early childhood loss or deprivation), biologic factors (e.g., alteration of neurotransmitters), and genetic predisposition are factors in the etiology of depression.

• Prior episodes of depression
• Family history of depression
• Prior suicide attempt(s)
• Female gender (lifetime risk, 20% to 25% for women and 7% to 12% for men)
• Age (rate of occurrence is highest from age 25 to 44)
• Postpartum period
• Medical comorbidity
• Stressful life events, especially loss
• Lack of social support system
• Current or past alcohol or drug abuse

Significantly depressed mood, diminished interest or pleasure in activities (including reduced sexual functioning), and at least four of the following.

• Feelings of worthlessness, self-reproach, inappropriate guilt
• Significant weight loss or weight gain
• Insomnia or hypersomnia (especially early morning awakening)
• Hyperactivity or inactivity
• Fatigue/loss of energy
• Poor concentration, restlessness, irritability, withdrawal
• Recurrent thoughts of death or suicide

• Bipolar I and II mood disorders (manic or hypomanic)
• Schizoaffective disorder
• Substance abuse or withdrawal (e.g., cocaine, amphetamines, caffeine)
• Medical illness (e.g., endocrine dysfunctions such as hypothyroidism, pancreatic cancer, other malignant neoplasms, central nervous system lesions, diabetes mellitus, vitamin deficiency)
• Normal life stress (e.g., bereavement)
• Delusional, adjustment, or anxiety disorder
• Dementia or malnutrition in the elderly

The facial expression and demeanor may appear withdrawn, sad, exhausted, or agitated. The physical appearance may include weight loss or gain.

A variety of laboratory tests can be abnormal with depression.

• Determine underlying medical conditions.
• Screen for biologic abnormalities (e.g., the dexamethasone suppression test to differentiate psychotic depression from schizophrenia; sleep EEG to differentiate sleep apnea from depression).
• Blood tests (e.g., measure neurotransmitter levels; screen for amino acid or folate deficiency).

The Hamilton Rating Scale for Depression (HAM-D) or Beck's Depression Inventory (BDI) are used to assess symptoms and severity of depression.

• Assess symptoms/degree of severity. This may include a clinician-completed rating scale, such as the HAM-D; a psychological test, such as the Minnesota Multiphasic Personality Inventory (MMPI); or a mental status examination, such as the Global Assessment Functioning Scale.
• Evaluate for concurrent substance abuse, medical conditions, or nonmood psychiatric conditions.
• Self-reported questionnaire, e.g., Beck Depression Inventory (BDI).

Depending on the type, number, severity, and duration of episodes one or more of the following are recommended.

• Pharmacotherapy
• Psychotherapy, including interpersonal and cognitive–behavioral psychotherapies
• Bright light treatment, for seasonal depression
• Nutritional support
• Yoga, exercise, meditation, massage, and tai chi may be helpful
• Hospitalization if suicide is possible

• Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac; 10 to 80 mg once a day) or sertraline (Zoloft; 50 to 200 mg once a day) block serotonin reuptake. Side effects are generally fewer than for MAOIs and tricyclic antidepressants but can include gastrointestinal upset, sedation, sexual dysfunction, and headache with a three day to two-week onset. SSRIs can be combined with tricyclics.
• Monoamine oxidase inhibitors (MAOIs) such as phenelzine (Nardil; 15 to 90 mg once a day) increase intrasynaptic norepinephrine levels. Severe side effects (e.g., hypertension) require a tyramine-free diet. Use of other antidepressants is contraindicated.
• Tricyclic antidepressants such as amitriptyline (Elavil; 50 to 300 mg once a day) increase the activity of norepinephrine. Side effects include xerostomia, constipation, and orthostatic hypotension with a two-week onset.
• Atypical antidepressants include drugs such as bupropion (Wellbutrin; 200 to 450 mg bid), a dopamine reuptake blocker; heterocyclics; and newer medications, such as venlafaxine (Effexor; 75 to 375 mg bid or tid), or mirtazapine (Remeron; 15 to 45 mg once a day).

Usually a combination of relaxation techniques, nutrition, and herbs provide the greatest relief.

• B12 and folate: Even with normal serum values, some patients respond well to supplementation. Particularly the elderly are at risk for deficiency, since proper digestion is required for good utilization. Dose is 800 mcg/day for folate and 100 to 500 mcg/day for B12.
• Other vitamins shown to be low in depression are vitamin C (1,000 mg tid), biotin (300 mcg), B1 (50 to 100 mg), B2 (50 mg), B6 (50 to 100 mg). Minerals shown to be deficient are calcium (800 to 1,200 mg), iron (15 to 30 mg), magnesium (400 to 800 mg). A good multi-vitamin can efficiently address these deficiencies. In addition, chromium (200 to 500 mcg) helps to stabilize mood changes associated with hypoglycemia.
• Essential fatty acids: depleted in depression (1,000 to 1,500 IU/day)
• Vanadium: Excess vanadium is associated with depression.

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, it is important to ascertain a diagnosis before pursuing treatment. Herbs may be used as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, teas should be made with 1 tsp. herb per cup of hot water. Steep covered 5 to 10 minutes for leaf or flowers, and 10 to 20 minutes for roots. Drink 2 to 4 cups/day. Tinctures may be used singly or in combination as noted.

• St. John's wort (Hypericum perforatum): Numerous studies support its use in mild to moderate depression; side effects may include photosensitization, gastric upset, headaches, and rash. Dose is 1 to 4 ml tincture/day, or 250 mg tid when taken as the only herb. It may take four to six weeks to become effective. Do not use concomitantly with an antidepressant agent.
• Valerian (Valeriana officinalis): sedative, with digestive problems
• Black cohosh (Cimicifuga racemosa): chronic depression, especially with a hormonal component
• Ginkgo (Ginkgo biloba): circulatory stimulant, especially with decreased circulation and/or memory loss
• Oatstraw (Avena sativa): nerve tonic, gentle, slow acting
• Siberian ginseng (Eleutherococcus senticosus): improves ability to withstand stress
• Licorice (Glycyrrhiza glabra): antidepressant, especially for long-term stress with a digestive and/or hormonal component. (Contraindicated in hypertension.)
• Passionflower (Passiflora incarnata): especially for emotional upheaval with nervousness and insomnia
• Lemon balm (Melissa officinalis): mild sedative and spasmolytic, especially with a "nervous stomach"

A combination of equal parts of four to six herbs (1 cup tea tid, or 30 to 60 drops tincture) listed above can be very helpful.

Although homeopathics can be very helpful, an experienced homeopath should be consulted for appropriate treatment based on constitutional type.

Recent studies show that acupuncture can be effective at relieving symptoms, at times statistically comparable to antidepressants or psychotherapy.

Therapeutic massage has been shown to be effective in increasing circulation and promoting general well-being.

Patients should be closely monitored for compliance, comorbidity, and side effects. Concurrent psychotherapy should be encouraged.

Education that compliance with regimen decreases the chance of relapse. Cognitive or psychotherapy directed at coping skills may help prevent relapses. Sleep, exercise, and good diet are important self-care steps that should be encouraged. Biofeedback, meditation, visualization techniques, and tai chi are effective ways to prevent or reduce the symptoms associated with depression.

• Drug interactions (e.g., combining of MAOIs and SSRIs) or drug overdose (e.g., tricyclics) can be severe or fatal.
• 20% to 25% rate of associated medical problems with depression.
• 15% of patients with major depressive disorder die from suicide.

The course of recurrence is variable. Fifty percent of patients who have suffered an initial episode suffer a second major depressive disorder, 70% of those suffer a third, and 90% of those suffer a fourth episode. Twenty-five percent of patients with depression develop a bipolar disorder. Untreated episodes of depression last 6 to 24 months. The need for pharmacologic and psychologic treatment is greater with subsequent episodes.

Preschool children whose mothers took tricyclic antidepressant drugs or fluoxetine during pregnancy showed no significant difference in global IQ or language and behavioral development.

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