Question

Are the selective serotonin reuptake inhibitors (SSRIs) effective in older depressed people, and how suitable are they in terms of their pharmacodynamics and pharmacokinetics? How safe are they and can they result in confusion and loss of memory if they are taken for several years?

Answer

The selective serotonin reuptake inhibitors (SSRIs) were developed especially for the treatment of depression. They are suitable for, and well tolerated by, older subjects and most studies suggest that they are as effective in treating depression as a tricyclic antidepressant. They are also safe in overdose and begin to act sooner than the tricyclics. Drugs in this class include fluvoxamine, fluoxetine, paroxetine and sertraline. They all seem to have similar beneficial effects on depression in older patients. Although they only represent a modest step forward in the treatment of depression in older patients, they are perhaps a better first choice than tricyclic antidepressants.

This is especially true when the patient has co-morbidities. The tricyclics have a strong anticholinergic profile which can result in several peripheral and central side effects, such as urinary restriction, impaired vision, dry mouth, memory deficits, and delirium. Newer substances such as the SSRIs, and also the selective noradrenaline reuptake inhibitors (SNRIs) and reversible monoamine oxidase inhibitors (RIMAs) seem to pose far less risk to patients susceptible to anticholinergic effects or with cardiovascular disturbances (i.e. many older patients).

The tricyclics and also the original (non-reversible) monoamine oxidase inhibitors would have serious consequences if taken in overdosage. However, having said all that, if one is careful with the dose and carefully monitors the patient, then these drugs are still effective and good treatments for depression, in older people as in younger people. The beneficial effect may take some time to occur, but many of the tricyclic antidepressants are very long acting and so can be taken once at night. In this way, side effects such as sedation may be used to advantage. Since there is still room for more research with the newer drugs, some doctors prefer to stick to using the older tricyclic antidepressants, which they know and have wide experience with. The tricyclics may certainly be the best choice for some patients and choice of drug should always take into account the individual.

Lofepramine is a conventional tricyclic antidepressant but it is relatively free of many of the side effects of the other tricyclic antidepressants. Furthermore the older person handles the drug in a very similar way to the younger person. However a word of caution; many of the studies done with lofepramine have involved small numbers of people and long term data are not available.

In general the same principals of drug treatment are true for old and young depressed patients. However, the bodies of older patients may not handle the drugs so easily, so that they get more of the drug in the blood for a given dose or may suffer more side effects from them. It is always wise therefore to start with the lowest dose and to increase it very slowly depending on the balance of the beneficial and the unwanted effects.

Although memory problems that develop in a patient taking SSRIs are unlikely to be due to the SSRI, the only way to be sure is to stop taking the drug (abrupt withdrawal should be avoided). The memory problems may be due to the depression itself, and would lift if that were treated fully. Or they may be a symptom of another underlying process such as dementia. The only satisfactory way to determine this would be for the patient to see a physician or psychiatrist for review.

Links

• General information on depression