Approximately 65% to 70% of depressed patients who take Prozac find that their symptoms are fully relieved within two to six weeks and that they are able to function normally once again. The other 30% to 35% of patients who don’t respond or who can’t tolerate the early side effects of nausea or insomnia that may occur for a couple of days in the beginning may respond instead to one of the older antidepressants; they may fall into the category of treatment-resistant (to all antidepressants); or they may respond to one of the new antidepressants such as Zoloft, Paxil, Effexor, Nefazodone or an antidepressant still being tested in research clinical trials and not yet on the market.

The other well-tried older antidepressants have similar rates of success, but side effects are almost always present and bothersome.

Many psychiatrists recommend augmentation treatment by adding lithium or a thyroid hormone, Cytomel. Oftentimes the addition of one or both of these drugs to the antidepressant boosts the patient out of depression. Both drugs are considered step-up treatments. However, if the psychopharmacological approach does not work, consider psychotherapy.

In extreme cases, in which the patient is suicidal, losing weight, or totally unresponsive to any of the above medication, electroconvulsive therapy has proved very useful. Despite the negative associations some people have about ECT, it is a proven therapy that rapidly and effectively treat serious depression.

Finally, patients who are treatment resistant to all medications on the market may wish to consider participating in a free clinical research trial on a new antidepressant compound that is being evaluated at a number of universities and clinical research centers.

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Yes. Certain types do seem to respond to Prozac more quickly and more positively. The transformations Prozac causes—and make no mistake, I have observed such transformations in depressed patients over the last thirty years—occur in a particular population. They happen with people who may be depressed and lethargic when they come into my office, but in the past have bad often undisclosed periods of higher energy—and the accomplishments to prove it These patients are not diagnosable manic-depressive. But they have a tendency in that direction, with perhaps only one or two symptoms of subclinical depression that affect their personalities and typically send them on a fruitless search for a cure through psychotherapy alone rather than medication. Yet some psychologists and psychiatrists, having failed to detect the subclinical depression or soft bipolar symptoms in the past or family history, misdiagnose these patients as having character or personality disorders only. Psychotherapy consists of focusing on drives and defenses—ignoring the formes frustes symptoms of mood disorders. In short, the correctable symptoms do not get treated.

These people often have a buried past of hyperthymia, a mildly “up” state with brisk energy, buoyant optimism, and an irritable temper. Hyperthymic people get a lot done and normally need only four to six hours’ sleep—like President Bill Clinton, who is most likely hyperthymic and constantly on the run. This is not an illness; it is an asset.

*85\22\4*

Patients who take antidepressants are often suicidal to begin with, and they continue to be at risk as the antidepressant agent is escalated. Eighty-six published and unpublished reports claim that in a small minority of patients, Prozac, like other antidepressants, is associated with an increased propensity toward suicidal thoughts.

The reasons for this are unclear, but one commonly held hypothesis is that during the first few weeks of treatment, the antidepressant is thought to boost the patient’s energy before it alters his or her mood, who the result that a patient who may have previously been too slowed down by depression to do anything dangerous can now act on impulse rather than remain in a state of lethargy and immobilization.

A number of studies indicate that in the retarded depressed patient—that is, the patient whose thoughts and movements are slowed down or retarded by the depression—the potential for suicide may temporarily increase as the depression lifts. Reports of this phenomenon have circulated in the psychiatric literature for decades.

Another possible explanation is that in a small number of depressed suicidal patients, the administration of Prozac increases anxiety, which could conceivably push the patient over the edge. This increased anxiety and recklessness can be easily monitored by a trained psychopharmacologist, and if necessary, the patient can be hospitalized. Most depression experts agree that when a depressed patient complains of active suicidal thoughts, it is a psychiatric emergency and hospitalization is immediately needed. This is not something to fear.

*65\22\4*

Prozac (fluoxetine) is easily absorbed after being swallowed, whether or not the patient has recently eaten. (However, the presence of food does slow down the process somewhat.) Once the medication is absorbed, it is metabolized primarily by the liver, which turns fluoxetine into its breakdown product (or metabolite), norfluoxetine. Both chemicals block the uptake of serotonin.

About a month after beginning treatment, the concentration of both fluoxetine and norfluoxetine reaches a stable level. Part of this stability derives from the fact that as an antidepressant Prozac has a long half-life, meaning that it takes a relatively long time to decrease by half its originally administered amount. The half-life of fluoxetine is one to three days, and the half-life of norfluoxetine ranges from seven to fifteen days – a long time compared to the other SSRIs on the market. Prozac lingers. An advantage to its long half-life is that patients who stop taking the drug, even abruptly, are unlikely to go through withdrawal, which often occurs with antidepressant drugs that have a shorter half-life. Similarly, a patient who forgets to take a pill for a day or two will not be plunged into despair as a result of the lapse.

On the other hand, sometimes you might not want Prozac to be in the body, perhaps because of a medical emergency that requires another drug. In switching to a MAOI, a patient has to wait up to five weeks, since the two drugs together can be lethal and are thus contraindicated. In that situation, the long half-life could conceivably be a disadvantage.

Prozac is excreted print with about 80% of the drug eliminated by the urine and 15% by the feces. Although more long-term studies need to be done, the process of absorption, metabolism, and excretion of Prozac seems to be the same in the elderly and in the young.

*43\22\4*

It depends on the individual. The evidence suggests that between 20% and 30% of patients have only a single depression in their lives. Four to six months after their depression has lifted, these patients can taper off Prozac without recurrence and may never have to take Prozac or another antidepressant again.

However, millions of people suffer from recurrent depression. These people are much better off taking Prozac or another antidepressant on a permanent basis to prevent future attacks. This is also true for those manic-depressive patients who are on lithium but who nonetheless find that the depressive phase still breaks through. For these people, lithium and Prozac or another antidepressant have to be taken together on a long-term basis.

Keep in mind, though, that older antidepressants have been around for thirty to thirty-five years. Although some patients have been successfully taking Prozac for as long as seven or eight years, Prozac is still essentially a new drug, and we simply do not know its long-term effects. There is still reason for caution.

Is it easy to withdraw from Prozac? Yes. If necessary, patients taking doses between 5 and 20 mg can stop taking the medication immediately. However, as a general rule in medicine, it is always better to taper off drugs. Patients taking higher doses can taper off over a week to ten days by taking smaller doses every other day and then every third day before discontinuing. Prozac’s – metabolism would suggest that coming off the medication should not be of concern due to the long half-life of the antidepressant, which means it is tapering off slowly by itself after it has been discontinued.

Does Prozac lose its effectiveness after continued usage? No, it does not. Once Prozac has sufficient time to build up in the body and relieve the symptoms of depression, the patient takes either the same dosage or less during both the continuation phase, which lasts two to three months, and later during the long-term maintenance phase.

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