Recently, the demand for medications to treat depression has increased: according to statistics, the number of patients receiving them in 2020 is 23% higher than in 2015. And due to the unstable economic situation in 2022, the demand for antidepressants is definitely not going to decrease.
But there are still a number of myths about antidepressants (even within the medical community). Let’s sort it out together.
Antidepressants are ineffective
Ineffectiveness is one of the most common myths about antidepressants. It is based on the fact that there are still gaps in the pathophysiology and mechanism of action of depression medications. Some researchers believe that the therapeutic activity of antidepressants is the result of side effects that increase patient expectations. A large-scale review of 15 studies involving more than 3,300 patients has dotted the i’s. Its results showed that participants without early adverse events who received citalopram or paroxetine had significantly greater relief of depression symptoms, as assessed by the Hamilton Depression Scale, than those who received placebo.
Impaired serotonin metabolism has nothing to do with the pathogenesis of depression, so selective serotonin reuptake inhibitors (SSRIs) are not pathogenic medications for its treatment
Some experts have long believed that the hypothesis about the effects of serotonin and its precursor 5-hydroxytryptophan on depression is nothing more than a tool for the pharmaceutical industry to promote a simplified biological model of this pathology and to stimulate the market for SSRIs. However, there is now evidence that decreased levels of 5-hydroxytryptophan in the brain can cause acute relapses in depressed patients.
Antidepressants only work while the patient is taking them, and the risk of depression relapse is not reduced once the course is completed
Studies with adult patients have shown that taking antidepressants, particularly tricyclic antidepressants (TCAs), SSRIs, and selective serotonin and norepinephrine reuptake inhibitors (SSRIs) can reduce the risk of relapse, although not completely prevent it. For example, relapse within 1 to 2 years occurred in 50% of patients receiving placebo and only 23% of those taking antidepressants. The results of a major review of 31 studies involving 4,410 patients showed that the effects of antidepressant treatment appear to persist for up to 36 months.
TCAs are practically never used in modern practice
The use of TCA began as early as 1959. With the advent of safer drugs, particularly SSRIs and SSRIsN, the demand for TCAs as antidepressants has actually declined. Today, SSRIs are the first-line treatment for depressive and several other psychiatric disorders. Nevertheless, TCAs remain relevant as therapy and prophylaxis for a number of other conditions.
Antidepressants are strictly contraindicated in pregnancy
The negative attitude toward prescribing antidepressants during pregnancy is related to TCAs, which appeared on the market around the time of the “thalidomide tragedy.” At that time, between 8,000 and 12,000 babies were born with malformations because of mothers’ use of thalidomide as a sleeping aid. However, with the advent of SSRIs, which have a favorable safety profile, the situation has changed.
SSRIs are similar in mechanism of action to TCAs
Indeed, SSRIs, like TCAs, inhibit the reuptake of the two leading neurotransmitters, noradrenaline and serotonin, by presynaptic neuronal terminations, causing monoamines to accumulate in the synaptic gap and enhancing postsynaptic impulsation.
Antidepressants may exhibit cardiotoxic effects
Prescription of antidepressants not only improves mental well-being, but also contributes to a reduction in the risk of cardiovascular disease. For example, the drugs of this group reduce the likelihood of recurrent cerebral ischemia in patients who have had a stroke, and repeated myocardial infarction. In addition, antidepressants appear to improve the survival of patients in the postinfarction period.
All antidepressants adversely affect sexual function
Several mechanisms may underlie sexual dysfunction during antidepressant use. First of all, it is sedation, which decreases libido, reduction of dopamine level, peripheral influence of neurotransmitters, which disturbs the balance of adrenergic and cholinergic system. Hormonal effects also play a role, in particular an increase in prolactin levels due to an increase in serotonin, as well as enzymatic effects such as induction of hepatic metabolism of testosterone, blocking nitric acid synthesis. In addition, depression itself can be a cause of erectile dysfunction.
SSRIs are active in drug interactions
Indeed, SSRIs inhibit enzymes of the CYP cytochrome system, which is associated with pharmacokinetic drug interactions. However, different drugs in this group differ significantly in their ability to inhibit individual CYPs. Thus, fluoxetine and paroxetine are potent inhibitors of CYP2D6 isoenzyme and can increase plasma concentrations and side effects of drugs that are primarily metabolized by this isoenzyme (eg, beta-blockers – carvedilol, metoprolol, propranolol, etc.). On the other hand, citalopram and escitalopram are weak CYP2D6 inhibitors and are less likely to have drug interactions.
A combination of SSRIs and SSRIs is inappropriate because the drugs in these groups exhibit similar pharmacological effects
According to the data available today, combinations of SSRIs and SSRIs may in fact be promising. Moreover, their components can enhance the action of each other. For example, synergism of venlafaxine and sertraline is established. It is explained by a simultaneous strengthening of influences on three key monoaminergic systems: serotonergic, noradrenergic, and dopaminergic. By enhancing the impaired monoaminergic neurotransmission in depression, the combination of SSRI sertraline and SSRI venlafaxine levels out most of the symptoms of depression. Moreover, pharmacological synergism allows for lower doses of venlafaxine and sertraline in combination, which minimizes the side effects and toxic risks of each drug.