DEPRESSION: WHEN ARE DRUGS CALLED FOR AND WHICH ONES SHOULD YOU USE?

Should Everyone Who Is Sad or Depressed Take Antidepressants?

Although depression is the most common mental illness in older adults, not everyone who is sad or depressed is a candidate for these powerful drugs.

Kinds of Depression

Drug-induced depression

Ironically, one of the kinds of depression that should not be treated with drugs is depression caused by other kinds of drugs. If someone is depressed and the depression started after beginning a new drug, it may well be drug-caused. Commonly used drugs known to cause depression include the following:

• barbiturates such as phenobarbital
• tranquilizers such as diazepam (VALIUM) and triazolam (HALCION)
• heart drugs containing reserpine (SER-AP-ES and others)
• beta-blockers such as propranolol (INDERAL)
• high blood pressure drugs such as clonidine (CATAPRES), methyldopa (ALDOMET), and prazosin (MINIPRESS)
• drugs for treating abnormal heart rhythms such as disopyramide (NORPACE)
• ulcer drugs such as cimetidine (TAGAMET) and ranitidine (ZANTAC)
• antiparkinsonians such as levodopa (LARODOPA) and bromocriptine (PARLODEL)
• corticosteroids such as cortisone (CORTONE) and prednisone (DELTASONE)
• anticonvulsants such as phenytoin (DILANTIN), ethosuximide (ZARONTIN), and primidone (MYSOLINE)
• antibiotics such as cycloserine (SEROMYCIN), ethionamide (TRECATOR-SC), ciprofloxacin (CIPRO), and metronidazole (FLAGYL)
• diet drugs such as amphetamines (during withdrawal from the drug)
• painkillers or arthritis drugs such as pentazocine (TALWIN), indomethacin (INDOCIN), and ibuprofen (MOTRIN, ADVIL)
• the acne drug isotretinoin (ACCUTANE)
• other drugs including metrizamide (AMIPAQUE), a drug used for diagnosing slipped discs, and disulfiram (ANTABUSE), the alcoholism treatment drug.[1]

The remedy for this kind of depression is to reduce the dose of the drug or stop it altogether if possible. If necessary, switch to another drug that does not cause depression.

Another major cause of drug-induced depression is alcoholism, the treatment of which is difficult.

Situational or reactive depression

Other causes of depression that should not be treated with antidepressant drugs are the “normal” reactions to life problems, such as the loss of a spouse, friend, relative, or job, or other situations that normally make almost anyone sad. If the depression is clearly a response to overwhelming life crises, antidepressants have little value. Other options, such as support from family and friends, psychotherapy with a mental health professional, or a change in your environment, are worth exploring.[2] Doing something nice for yourself, talking with a friend, and exercising every day can help you get through these difficult situations.

Medical conditions that can cause depression

Older adults (or anyone) who appear depressed may have a thyroid disorder, a type of cancer—such as pancreatic, bowel, brain, or lymph node (lymphoma)—viral pneumonia, or hepatitis.[3] In addition, there is evidence that people who have had a stroke or who have Parkinson’s disease or Alzheimer’s disease may become depressed and, in some cases, may respond to antidepressant drugs.

A major depressive episode: the kind that will usually respond to drugs

If a depressed mood accompanied by several of the following problems has been present for at least several weeks, and a careful history, physical exam, and lab tests have ruled out specific causes of depression, true primary depression is probably the diagnosis. The problems are sadness that impairs normal functioning, difficulty concentrating, low self-esteem, guilt, suicidal thoughts, extreme fatigue, low energy level or agitation, sleep disturbances (increased or decreased), and appetite disturbance (increased or decreased) with associated weight change.[4] Since suicidal thoughts and attempts often characterize depression, the possibility of suicide using antidepressant drugs has to be kept in mind and only a small number of pills (see How to Reduce the Adverse Effects of Antidepressants) prescribed at one time. Another way of describing the pervasive nature of this kind of severe depression is that the person displays—and relates if asked—a sense of “helplessness, hopelessness, worthlessness and uselessness...as well as intense feelings of guilt over real or imagined shortcomings or indiscretions.”[5]

Although depression in older adults is usually unipolar (depression alone), occasionally there is a bipolar pattern with alternation of depression and mania. The latter shows up as an elated mood, rapid flow of ideas, and increased “energy.” The patient, often seeming hyperactive during this manic phase, can be intrusive, have an infectious sense of humor, and may show poor judgment in business or personal affairs, not infrequently going on spending sprees.[6] Lithium (ESKALITH, LITHOBID, LITHONATE) is often used successfully to treat people with bipolar disease. Other drugs approved for treatment of bipolar depression include olanzapine (ZYPREXA) and quetiapine (SEROQUEL).

Serious depressive illness is far less frequent in the elderly. According to data from the National Institute of Mental Health, while nearly 4% of people age 25 to 44 have had a major depression recently, fewer than 1% of people 65 and over have had this misfortune. In spite of this, about one-third of antidepressants are prescribed for people 60 and over even though they make up just one-sixth of the population.

Some of this apparent “overtreatment” may be due to failing to diagnose drug-induced depression and instead using a second drug to treat the depression caused by the first.

Other Uses—Usually Inappropriate—for Antidepressants

In addition to drug-induced depression, medical conditions that can cause depression, and situational or reactive depression—none of which merit treatment with antidepressants—there are other circumstances in which antidepressants are inappropriately dished out. In one community-based study, more than 50% of older people who had been taking antidepressants for a year or more had been started without a clear history of depression. Of these, one-half (or one out of four of all people using antidepressants) were using antidepressants as a sleeping pill, and others were given the drugs as alternatives to tranquilizers.[7] In view of the significant adverse effects of these drugs, their use for such purposes will cause risks that will outweigh the benefits even though, unlike benzodiazepine tranquilizers, they do not cause addiction.

In many countries, including the United States, there has been an extraordinary increase since 1990 in the use of antidepressants, mainly the SSRIs (selective serotonin reuptake inhibitors) such as fluoxetine (PROZAC) and paroxetine (PAXIL). This increase, more than twofold in the 1990s in the United States has been much larger than the smaller decrease in the use of older antidepressants.[8]

A survey in the United States of almost 6,000 people between the ages of 15 and 54 found that primary care physicians were much more likely than psychiatrists to prescribe antidepressants, tranquilizers, or sleeping pills for patients who did not have mood or anxiety disorders. Primary care doctors prescribed antidepressants to 22% of people, tranquilizers to 17% of people, and sleeping pills to 13% of people without mood or anxiety disorders. The author concluded that “primary care physicians are less selective in their use of psychoactive medicines, perhaps because of lower sensitivity and specificity of diagnoses in primary care settings.”[9]

What Are the Best and Worst Treatments for Severe Depression?

Everyone with the kind of severe depression described above should be evaluated by a mental health professional to determine what kind of psychotherapy would best supplement the antidepressant drugs that are going to be used.

The decision as to which drug is best will depend largely on which one has the fewest adverse effects, since all antidepressants are equally effective.[6] If depression has occurred previously and responded to one of the drugs without too many adverse effects, that would be the best one to try first. Otherwise, the table below compares the 11 tricyclic antidepressants that are listed on this web site as well as fluoxetine (PROZAC) and bupropion (WELLBUTRIN).

The Main Risks of Antidepressant Drugs

The four most common groups of adverse effects are anticholinergic, sedative, hypotensive (blood-pressure-lowering), and those effects on heart rate or rhythm. Two serious risks arising from the adverse effects are hip fractures and automobile crashes.

Hip fractures

A study of 1,021 older adults with hip fractures found that 14% of these life-threatening injuries are attributable to the use of mind-affecting drugs, including sleeping pills and minor tranquilizers, antipsychotics, and antidepressants.[10]

There are approximately 227,000 hip fractures each year in the United States, virtually all in older adults.12 Since the above study found that 14% of hip fractures are drug-induced, this means that if the results of the study are projected nationally, approximately 32,000 hip fractures a year in older adults are caused by the use of mind-affecting drugs. Approximately 60% of these drug-induced hip fractures are caused by antidepressant drugs.

The SSRI antidepressants such as fluoxetine (PROZAC, SERAFEM), sertraline (ZOLOFT), and paroxetine (PAXIL) are promoted as having fewer adverse effects than the older tricyclic antidepressants such as amitriptyline (ELAVIL) and imipramine (TOFRANIL, TOFRANIL PM). Canadian researchers recently reported that the SSRIs do not offer any advantage over the older antidepressants with regard to the risk of hip fracture.[11]

Automobile crashes that cause injury

A study involving 495 automobile crashes in older drivers in which an injury occurred found that a significant number of such crashes in older adults aged 65–84 were attributable to the use of benzodiazepine tranquilizers and tricyclic antidepressants. The study was particularly impressive because its findings were strengthened by observing that the rate of crashes that caused injury increased in the same group of people when they were using these drugs as opposed to when they were not using the drugs. The majority of the excess number of auto crashes that caused injury were attributable to the benzodiazepines. The authors, stating that the study findings may be generalizable to the population at large, found that if the association is causal, at least 16,000 auto crashes that caused injury each year in older drivers are attributable to psychoactive drug use (specifically benzodiazepines and tricyclic antidepressants), out of the 217,000 crashes that caused injury that occur each year among elderly drivers.[12]

Sedative effects

Most older adults who think they have a sleeping problem do not have the kind of severe depression that justifies the use of these drugs. (See discussion of nondrug treatments for sleeplessness.) Nevertheless, if the sleep disorder is a consequence of severe depression, the “adverse effect” of sedation may be useful as long as it does not produce too much sedation, with the risk of falling. This is an important consideration especially in people who already have some impairment of thinking, increased confusion, disorientation, and agitation.[13]

Hypotensive effects: lowering of blood pressure to levels that are too low

Orthostatic (postural) hypotension, or the fall in blood pressure that occurs when someone stands up suddenly, is a common adverse effect of antidepressants, especially in older adults. It can be even more troublesome if the person is already at increased risk for this problem because he or she is taking other drugs to treat high blood pressure. As a result of such a drug-induced drop in blood pressure, falls that result in injury, heart attacks, and strokes can occur. For this reason, before starting treatment with one of these antidepressants, blood pressure should be taken both in the lying position and after standing for two minutes. This should be repeated after using the drug for several weeks.

Drug-induced parkinsonism

Like the antipsychotic drugs, many antidepressants can also cause drug-induced parkinsonism, although this is less common with most antidepressants. Drug-induced parkinsonism involves the following symptoms: difficulty speaking or swallowing; loss of balance; masklike face; muscle spasms; stiffness of arms or legs; trembling and shaking; unusual twisting movements of the body.

Effects on heart rate and rhythm

These drugs can cause the heart to speed up. This is more of a problem with older antidepressants (see table below). They can also cause a slowing down in the conduction of electricity through the heart, which is especially dangerous if someone already has heart block.[13] For this reason, a baseline electrocardiogram should be taken before starting any antidepressant therapy.

Mania induced by selective serotonin reuptake inhibitors (SSRIs)

All currently available antidepressant drugs appear able to induce hypomanic and manic reactions.[14],[15] This is a serious concern for people taking the serotonin reuptake inhibitor group of antidepressants, which includes the SSRIs such as fluoxetine[16] but also the antidepressants such as nefazodone that have a combined effect on serotonin and norepinephrine reuptake.[14] This reaction can be severe, having psychotic features or requiring patients to be secluded for extreme agitation.[16]

As can be seen from the table above, the drugs with the fewest overall adverse effects in older adults are desipramine (NORPRAMIN), which has a “mild” for all four kinds of adverse effects, and nortriptyline (AVENTYL, PAMELOR), which is “mild” for three of the four. Fluoxetine (PROZAC) and bupropion (WELLBUTRIN) may have as few or fewer adverse effects than desipramine and nortriptyline, but adequate comparative studies on older adults have not yet been published. The drug with the worst adverse effects profile in older adults is amitriptyline (ELAVIL), with “strong” adverse effects for three of the four categories. We list this drug as Do Not Use.

If the adverse effects of whichever drug is selected are too severe, or if the drug does not seem to be working, talk to your doctor about switching to a drug less likely to cause the troublesome effects.

Increased suicide risk in adults and children

In early 2004, the FDA issued a public health advisory warning, which stated that in studies of depressed adults and children being treated with antidepressants there was an increased risk of suicidal thoughts and actions.[18]

The drugs implicated are bupropion (WELLBUTRIN), citalopram (CELEXA), fluoxetine (PROZAC), fluvoxamine (LUVOX), mirtazapine (REMERON), nefazodone (SERZONE), paroxetine (PAXIL), sertraline (ZOLOFT), escitalopram (LEXAPRO), and venlafaxine (EFFEXOR). It should be noted that the only drug that has received approval for use in children with major depressive disorder is fluoxetine. Several of these drugs are approved for the treatment of obsessive-compulsive disorder in pediatric patients, for example, sertraline, fluoxetine, and fluvoxamine. Fluvoxamine is not approved as an antidepressant in the United States.

The possibility of an increased risk of suicide in patients taking antidepressants is not new. In 1991, Public Citizen’s Health Research Group petitioned the FDA to require a black-box warning in the labeling for fluoxetine (PROXZAC) about the risk of suicide.[19] Unfortunately, the petition was denied. However, in 2004, the FDA requested that black box warnings be given to all antidepressants to inform consumers about the risk of increased risk of suicide in children and adolescents. In 2007, the agency expanded the warning to include young adults (ages 18-24).

How to Reduce the Adverse Effects of Any of These Antidepressants

• Have a baseline electrocardiogram and blood pressure taken before starting.[2]
• Start with a dose of one-third to one-half the usual adult dose, meaning 15–25 milligrams a day, at bedtime. Increase the dose very slowly.[2] It may take three weeks to see an effect. A trial with one of these drugs, should continue until it either works or causes persistent adverse effects.[3]
• Get a prescription for only one week’s worth of pills, since more pills increase the chance of a successful suicide attempt by people who are severely depressed.[6] This is much less likely to be a problem with newer antidepressants such as SSRIs or buproprion.
• Lower the dose gradually, as symptoms dictate, after successful treatment for several months.[13] 

It is important to realize that long-term treatment with antidepressants is not always necessary even when the drug is being used to treat the kind of serious depression for which its use is proper. In one study, after patients had been successfully treated for four months with antidepressants, half were continued on their drugs and the other half were switched to a placebo. After an additional two months, most of the patients—on either the actual drug or the placebo—were still doing well; only about one-fourth, the same in both groups, had relapsed.[20]

Other recommendations for more effective and safer use of these drugs include:[7]

1. When starting a drug for a specific depressive illness, the doctor should monitor your response carefully to see if a different dose (or drug) should be used.
2. It should be made clear to you that depression can be an episodic illness, that recovery is expected, and that the treatment will probably eventually be stopped.
3. If treatment with drugs is started as a trial in possible depression, you should be informed that it is a trial and that treatment will continue for a specified time, depending on the response of key symptoms.
4. The possibility of adverse effects should be evaluated carefully before these drugs are used primarily as sleeping pills or as an alternative to tranquilizers in the elderly.