By: Anat Ziv with Prof. Ehud Klein, Director, Division of Psychiatry, Rambam Medical Center


It’s been almost twenty years since Prozac came into our world, positioning depression at the center of the consensus of western culture. Within its first two years on the market, Prozac broke sales records that only Viagra succeeded in breaking. It was the first in the generation of new antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs) (see box).
Prozac, with its various derivatives, has already become a part of our lives, like plasma TV and sushi. However, despite 20 years of widespread use as a first line antidepressant treatment, despite revolutionizing our thinking about depression in general and about antidepressants in particular, the exact mechanism of these drugs’ action on brain cells is not yet clear. But, apparently, it works so well that nobody is really bothered by this fact - neither doctors nor patients. Otherwise, how could one explain this amazing data; 2.3 million (!) prescriptions for antidepressants were written in Israel only during the last year.
However, to ensure the efficacy of these drugs, there are several other things that are important to know with respect to the way they work, in order to secure the aim - the success of the treatment. Otherwise, the treatment may fail and the depression will remain. “In the past, we were satisfied with the fact that the condition of the patient improved,” explains Prof. Ehud Klein, Director of Division of Psychiatry, Rambam Medical Center. “Today our goal is a complete improvement, that is, a total eradication of the depression. The data show that a large proportion of patients experience partial improvement. If the improvement is not complete, it is very likely that the depression will recur.”

This is not Optalgin

This is perhaps the most widely known fact about the new antidepressant drugs: they require three to six weeks to elicit an effect. They don’t work like Optalgin - you take the tablet and the problem disappears. They must be given time in order to have an effect.

The first tablet

New studies in the field show that there is a chance that the first drug you take will not be the last. The chance of improvement with the first drug, after taking it properly (4-6 weeks), is around 40%. That is, 60% of patients will need to begin treatment with a second drug.

How do we know that this is really the right drug?

Prof. Klein: “When the drug is appropriate - we expect that within two-three months, the patient will feel good and the depression will disappear.”

Give them time

Despite their categorization as "user-friendly" drugs, they, too, may have side effects. One of them is sexual dysfunction. The drugs do not cause impotence, rather, the dysfunction involves a reduction in sexual desire, in the ability to enjoy oneself and reach orgasm, for both men and women. Additional side effects are excessive perspiration, constipation, and sometimes weight gain.
“There is no danger in these effects, and they disappear as soon as the treatment is stopped,” explains Prof. Klein. “The problem is that the side effects appear at the beginning of the treatment, before the positive effect of the drug is manifested. If this is not explained to the patient and he is not prepared for these effects, a negative balance is formed - he is not yet benefiting from the drug, but is already suffering from the side effects. Many patients take the drug for a few days, don’t see any positive effect, and then stop the treatment because of side effects causing discomfort.”

Don’t stop even if you feel good

Depression tends to be transient in most people. There is a difference between the first depression and recurrent depression, but in most cases, depression will generally disappear, even without treatment, within six to nine months. This is the natural course of the depression wave. Here comes the additional obstacle to drug therapy. “A person who started therapy one or two months ago, where the treatment is indeed helping,” explains Prof. Klein, “is still within the curve of the wave. If he stops taking the drug a month after feeling an improvement, he may still be within the natural course of the depression, he won’t feel any change, and the depression will return. We therefore recommend that the treatment continue for a period of about a year. This is the stage of maintenance or of preventive therapy, which is important to reduce the likelihood that the depression will recur.”
“However, it is difficult to persuade people to take drugs despite the fact that they’re feeling good. This is the stumbling block, because if they don’t continue taking the drug, the depression might recur.”

Till when?

Depression is a disease that tends to recur. Statistically, about 70% of people who experienced a depressive event will experience another event. “For those people in whom this tendency recurs two or three times,” explains Prof. Klein, “the standard approach is to give the treatment as long term preventive therapy.” What is long term? This will be considered separately in each case. It does not have to be for life.
“The problem is, as in all chronic conditions, that it is difficult to persuade people to continue the treatment. This treatment is designed to maintain balance, not to cure completely, and it must be continued to keep the situation under control. In certain cases, the depression is caused by life events, such as divorce, loss of a dear person, dismissal from a job, etc. In such cases, disappearance of the cause might lead to the disappearance of depression, with no recurrence.”
 
If depression tends to pass, why intervene?

Prof. Klein: “Pneumonia also passes without antibiotic treatment in some patients, but some may die. Furthermore, depression is associated with suffering and distress which can be spared and prevented. About 15% of people suffering from depression commit suicide, which is something that is, of course, important to prevent.”

Stop gradually

When the decision is made to stop the treatment, it is very important to do so gradually. This is to enable the monitoring of changes in the situation and reinstate the treatment as soon and as quickly as possible, in the event that the depression recurs.
Prof. Klein: “In addition, a long term treatment which is stopped suddenly may lead to effects similar to withdrawal symptoms for a short period of a week or two. The symptoms are usually mild, unlike narcotic drug withdrawal symptoms.”

No mixing

An additional problem of drug therapy was diagnosed in patients consuming addictive substances, such as alcohol and stimulants. Some of them stop using these substances when beginning treatment, but the moment they feel better, they stop the treatment and go back to the addictive substances.
Prof. Klein: “The combined effect of alcohol and antidepressant or anti-anxiety medications produces adverse responses. It can interfere with the effects of the medication on one hand, and to increase the effects of the alcohol or the drugs on the other. Furthermore, it is known that some of the drugs themselves, cocaine, for example, cause depression.

All or nothing

In order to ensure the success of the treatment, it is necessary to comply with the instructions for use. “If you take half the dose, for example,” explains Prof. Klein, “it impairs the treatment and renders it ineffective. With most of the new generation of drugs, it is sufficient to take them once a day - but every day.”