Depressive disorders may either be unipolar (depression alone) or bipolar (depression alternating with periods of extreme excitation). The formal diagnosis requires a cluster of symptoms, lasting at least two weeks.
These symptoms include, but are not limited to, mood changes, insomnia or hypersomnia, and diminished interest in daily activities.
The symptoms are not caused by any medical condition, drug side effect, or adverse life event. The condition is severe enough to cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
Secondary depression, or depression caused by unfavorable life events, is normally self limiting, and may best be treated with cognitive/behavioral therapy rather than drugs.
Antidepressant agents act by increasing the levels of excitatory neurostransmitters, or nerve cell chemicals that act as messengers in the brain’s nervous system. In 2003, a report showed that in addition to treating depression, use of antidepressant drugs may protect the brain from damage depressive episodes cause to the hippocampus, the area of the brain involved in learning and memory. Antidepressant drugs may be prescribed as a first-line treatment for depression, or in conjunction with other methods of controlling depression, such as behavioral therapy and exercise.
The main types of antidepressant drugs in use today are listed below, though the drugs available change frequently. For example, in mid-2003, the manufacturer of Wellbutrin released Wellbutrin XL, the only once-daily norepinephrine and dopamine reuptake inhibitor for treating depression in adults.
tricyclic antidepressants, such as amitriptyline (Elavil), imipramine (Tofranil), nortriptyline (Pamelor)
selective serotonin reuptake inhibitors (SSRIs or serotonin boosters), such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft)
monoamine oxidase inhibitors (MAO inhibitors), such as phenelzine (Nardil), and tranylcypromine (Parnate)
tetracyclic compounds and atypical antidepressants which do not fall into any of the above categories
Selective serotonin reuptake inhibitors maintain levels of the excitatory neurohormone serotonin in the brain. They do not alter levels of norepinephrine. These have become the drugs of choice for a variety of psychiatric disorders, primarily because of their low incidence of severe side effects as compared with other drugs in this therapeutic class. SSRIs show similar actions and side effect profiles, but may vary in duration of action.
Tricyclic compounds, identified by their chemical structure containing three carbon rings, are an older class of antidepressants. Although generally effective, they have a high incidence of anticholinergic effects, notably dry mouth and dry eyes, which can cause discomfort. They also cause cardiac arrythmias. Because tricyclics act on both serotonin and norepinephrine, they may have some value in treatment of patients who fail to respond to SSRIs. Drugs in this class often are available at low prices, which may be significant when cost is a major factor in treatment. They also have been found useful in control of some neurologic pain syndromes.
Tricyclic antidepressants are similar, but may vary in severity of side effects, most notably the degree of sedation and the extent of the anticholinergic effects.
Tetracyclic compounds and atypical antidepressants are chemically distinct from both the major groups and each other. Although maprotilene (no brand name, marketed in generic form only) and mirtazepine (Remeron) are similar in chemical structures, they differ in their balance of activity on serotonine and norepinephrine levels.
Monoamine oxidase inhibitors (phenelzine [Nardil], tranylcypromine [Parnate]) have largely been supplanted in therapy because of their high risk of severe adverse effects, most notably severe hypertension. They act by inhibiting the enzyme monoamine oxidase, which is responsible for the metabolism of the stimulatory neurohormones norepinephrine, epinephrine, dopamine, and serotonin. The MAOIs are normally reserved for patients who are resistant to safer drugs. Two drugs, eldepryl (Carbex, used in treatment of Parkinson’s disease) and the herb, St. John’s wort, have some action against monoamine oxidase B, and have shown some value as anti-depressants. They do not share the same risks as the non-selective MAO inhibitors.
All antidepressant agents, regardless of their structure, have a slow onset of action, typically three to five weeks. Although adverse effects may be seen as early as the first dose, significant therapeutic improvement is always delayed. Similarly, the effects of antidepressants will continue for a similar length of time after the drugs have been discontinued.
Dose varies with the specific drug and patient. Specialized references or a physician should be consulted.
Antidepressants have many significant cautions and adverse effects. Although a few are listed here, specific references should be consulted for more complete information.
SSRIs. The most common side effect of SSRIs is excitation and insomnia. Excitation has been reported in over 20% of patients, and insomnia in 33%. Significant weight loss has been frequently reported, but most commonly in patients who are already underweight. A 2003 report showed that SSRIs also increase the risk of upper gastrointestinal tract bleeding. SSRIs may cause some sedation, and patients should be cautioned not to perform tasks requiring alertness until they have evaluated the effects of these drugs. SSRIs are pregnancy category C drugs. In 2003, a new report demonstrated that late-term (third trimester) use of these drugs could cause neurological symptoms in newborns, including tremor, restlessness and rigidity. Most SSRIs are excreted in breast milk, and there have been anecdotal reports of drowsiness in infants whose mothers were taking SSRIs while breastfeeding.
Most notably, a joint panel of the U.S. Food and Drug Administration (FDA) issued strong warnings to parents and physicians in 2004 about the risk of suicidal behavior in children and adolescents taking SSRIs.
Tricyclic antidepressants. Amoxepine (not marketed by brand, generic available), although a tricyclic antidepressant rather than a neuroleptic (major tranquilizer), displays some of the more serious effects of the neuroleptics, including tardive dyskinesias (drug induced involuntary movements) and neuroleptic malignant syndrome, a potentially fatal syndrome with symptoms including high fever, altered mental status, irregular pulse or blood pressure, and changes in heart rate. These adverse effects have not been reported with other tricyclic antidepressants.
The most common adverse effects of tricyclic antidepressants are sedation and the anticholinergic effects, such as dry mouth, dry eyes, and difficult urination. Alterations in heartbeat also are common, and may progress to congestive heart failure, stroke, and sudden death.
Tricyclic antidepressants are in pregnancy categories C or D, although there have been no formal studies of the drugs on fetal development. There are no studies of effects on newborns, but some anecdotal reports of malformations have resulted from animal studies. The drugs are excreted in breast milk.
Monoamine oxidase inhibitors. The greatest risk associated with these drugs is a hypertensive crisis which may be fatal and most often occurs when the drugs are taken with interacting foods or drugs. More common adverse reactions may include low blood pressure and slowing of heartbeat. Sedation and gastrointestinal disturbances also are common. MAOIs are in pregnancy category C. Safety in breast feeding has not been established.
Tetracyclics and atypicals. Because these drugs are individual, there are no group patterns of adverse reactions. Specific references should be consulted.
The antidepressants have many drug interactions, some severe. Although a few are listed here, specific references should be consulted for more complete information.
SSRIs should not be administered with MAOIs. A wash-out period of about four weeks should be allowed before switching from one class of drugs to the other, five weeks if switching from fluoxetine (Prozac) to an MAOI.
MAOIs have many interactions, however the best known are those with foods containing the amino acid tyramine. These include aged cheese, chianti wine, and many others. Patients and providers should review the MAOI diet restrictions before using or prescribing these drugs. Because of the severity of MAOI interactions, all additions to the patient’s drug regimen should be reviewed with care.
Tricyclic compounds have many interactions, and specialized references should be consulted. Specifically, it is best to avoid other drugs with anticholinergic effects. Tricyclics should not be taken with the antibiotics grepafloxacin and sprafloxacin, since the combination may cause serious heart arrythmias.
Tricyclic compounds should not be taken with the gastric acid inhibitor cimetidine (Tagamet), since this increases the blood levels of the tricyclic compound. Other acid inhibiting drugs do not share this interaction.
SSRIs interact with a number of other drugs that act on the central nervous system. Care should be used in combining these drugs with major or minor tranquilizers, or with anti-epileptic agents such as phenytoin (Dilantin) or carbamazepine (Tegretol). In 2003, one of the biggest concerns regarding new prescriptions for tricyclic antidepressants was data concerning overdoses from these drugs. Information in Great Britain showed that this class of antidepressants was responsible for more than 90% of all deaths from antidepressant overdose. Physicians were being advised to prescribe SSRIs in new patients, but not to change the course of those who had taken tricyclics for years with success.
Cognitive behavioral therapy
A type of psychotherapy in which people learn to recognize and change negative and self-defeating patterns of thinking and behavior.
A mental condition in which people feel extremely sad and lose interest in life. People with depression also may have sleep problems and loss of appetite and may have trouble concentrating and carrying out everyday activities.
A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies; or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies; or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.
For Your Information
“Antidepressant Drugs May Protect Brain from Damage.” Mental Health Weekly Digest (August 18, 2003): 2.
“FDA Approves Once-daily Supplement.” Biotech Week (September 24, 2003): 6.
“FDA Panel Urges Stronger Warnings of Child Suicide.” SCRIP World Pharmaceutical News (February 6, 2004): 24.
“GPs Told Not to Prescribe Tricyclics.” Pulse (October 13, 2003): 1.
“Late-term Exposure to SSRIs May Cause Neurological Symptoms in Babies.” Drug Week (August 8, 2003): 255.
“SSRIs Increase the Risk of Upper GI Bleeding.” Psychiatric Times (July 1, 2003): 75.
Gale Encyclopedia of Medicine, Published December, 2002 by the Gale Group The Essay Author is Samuel D. Uretsky, PharmD.