Dr. Grossi's Blog


Dr. Philip Grossi
Tuesday, 27 March 2012

Antidepressants are among the most commonly prescribed medications in psychiatric practice.  There are six classes of antidepressants (NDRIs, NRIs, SNRIs, SSRIs,TCAs and MAOIs) which relate to either their mechanism of action or specific chemical structures.  The ones that share a common chemical structure such as TCAs (tricyclics - they all have a three ring chemical structure) are called a family of drugs; those that share a common method of action such as the SSRIs ( selective serotonin reuptake inhibitors) but do not have a chemical family resemblance are technically called a drug series. 

When I prescribe an antidepressant, I always consider the mechanism of action because the mechanism is apt to be associated with individual differences in response as well as tolerability and safety issues as well as degree of adherence due to differential side effect profiles. All are reuptake blockers except for MAOIs which are enzyme inhibitors. Some agents have multiple modes of action, which tends to increase their efficiency but also tends to increase their incidence of side effects which is the usual way that patients sense a difference in mechanism of action. Also, family history of efficacy with a particular agent may herad a genetic predisposition to respond to a particular mechanism of action.

Neurotransmitter reuptake inhibitors tend to have a delayed therapeutic effect which occurs in the folllowing manner.  They increase the neurotransmitter in the synapse, which stimulates a negative feedback mechanism that requires desensitization of postsynaptic neurotransmitter receptors.  This process does take time, sometimes as long as 6 weeks, though usually in two weeks some sense of progress is appreciated. Antidepressants with a different mechanism of action such as the MAOIs uncouple these series of changes and can produce a faster onset of action.

illustration to antidepressants blogWhile therapeutic benefits are often delayed, adverse effects tend to show up quickly. The most common acute effects are gastrointestinal (nausea, vomiting, diarrhea, constipation), sleep problems (insomna or sedation), behavioral (stimulation or activation), and headache. Many of these abate within a week spontaneously or can be treated quickly and easily.  Chronic side effects tend to include sexual side effects, weight gain, sleep disturbance and fatigue, and emotional dulling.

Weight gain and sexual dysfunction are the two most problematic side effects.  SSRIs, SNRIs, TCAs, and mirtazapine are associated with weight gain.  NDRI and phenylethylamine MAOIs are weight-neutral or even cause weight loss. Nefazodone appears to be weight-neutral. With regard to sexual dysfunction, antidepressants that stimulate serotonin inhibit at least desire, arousal, and orgasm. Serotonin may also reduce the excitatory neurotransmitters dopamine and norepinephrine and reduce the bioavaailability of testosterone and possibly the release of prolactin leading to other effects on sexual function.

(Consider a related post Are antidepressants expensive placebos?)