Antidepressants are one of the most widely used classes of drugs today. In Europe and the United States, 6-10% of the population is taking this class of medication. However, antidepressants can also cause a host of troublesome side effects that can affect treatment adherence; this percentage is high, estimated to be between 31-60%, and is influenced by trade-offs between benefits and harms. In fact, prescribers grossly underestimate the adverse effects of antidepressants: more than 80% of patients experience at least one adverse effect, and on average, each patient suffers from four adverse effects at the same time, many of which pose significant problems for patients and even affect daily functioning. Not surprisingly, for about 20% of patients, the use of antidepressants does more harm than good.
The newer antidepressants do show some potential for reducing adverse drug reactions compared to the more ancient tricyclic antidepressants (TCAs); however, not completely eliminated. A survey included 225 patients taking different types of antidepressants, and the adverse effects experienced by these patients while taking the medications and their percentages are shown below.
I. Jitteriness syndrome
This term is not well defined, but is quite common in clinical work: anxiety, agitation and irritability symptoms are worse in patients at the beginning of antidepressant treatment than before. It is estimated that up to 65% of patients experience these conditions when they start taking 5-HTergic or noradrenergic antidepressants. The significance of this phenomenon is that treatment may be discontinued if patients are led to believe that the medication may worsen their condition. Slow dosing can be effective in preventing this symptom, especially in patients with anxiety symptoms. Given the self-limiting nature of this phenomenon, waiting for tolerance to improve or temporarily combining benzodiazepines and propranolol may also be effective.
Other side effects
Gastrointestinal symptoms
Nausea occurs in 25% of patients shortly after taking a new antidepressant. This complaint was more common in patients taking venlafaxine and SSRIs, while bupropion, mirtazapine, and reboxetine were relatively uncommon. In the majority of cases, symptoms fade after 2-3 weeks, but in one-third of patients, the symptoms can persist. Splitting the dose, taking it with food or scheduling most of the dose before bedtime can help reduce this symptom, as can eating foods containing ginger and taking ranitidine and omeprazole. In addition, adding a low dose of mirtazapine to the treatment regimen may be equally effective.
About 15% of patients may develop diarrhea while taking the drug. Antidiarrheal medications may be useful, but for patients with persistent symptoms, a change in medication should be considered. 5% of patients with constipation may be more physically active, drink more water and eat more fiber, and use laxatives if necessary.
Weight gain
Weight gain is another common adverse effect of long-term antidepressant use. Some antidepressants can cause a transient weight loss at the beginning of the course of the medication, followed by weight gain during maintenance therapy. Most antidepressants cause only mild weight gain, but not mirtazapine, amitriptyline, and paroxetine. Bupropion is the only antidepressant that reduces body weight.
There are several options for dealing with this condition, including nutritional counseling and increased exercise, but in many cases, patients will need to change antidepressants. If a change is not possible, a combination of bupropion or a neuroleptic may be considered. Prior to antidepressant treatment, patients who are at higher risk of weight gain should be advised to avoid energy-dense foods.
Sweating
Excessive sweating is present in 20% of patients taking antidepressants, mainly on the scalp, face, neck and chest, often in paroxysms, throughout treatment. Patients taking reboxetine, venlafaxine and bupropion were more susceptible to these phenomena, while those taking paroxetine and mirtazapine were less likely to experience them. Based on hypotheses addressing their mechanisms, a variety of medications are used to treat excessive sweating, including 5-HTergic antagonists such as cycloheximide; anti-adrenergic drugs such as colistin; and anticholinergic drugs such as phenytoin and gronobrine.
Sexual dysfunction
Antidepressants can affect various aspects of sexual function, resulting in decreased libido, difficulty with sexual arousal, delayed ejaculation, sensual deficit, and erectile dysfunction. The incidence of these adverse reactions can be up to 80%. Patients taking SSRIs are more likely to experience sexual dysfunction than norepinephrinergic drugs. For some patients, these adverse effects may disappear or diminish with dose reduction. If you are taking a short half-life antidepressant, such as sertraline or paroxetine, consider a “drug holiday,” such as not taking the drug for several days, which can improve sexual function and satisfaction with sex in half of patients.
Sildenafil and tadalafil are effective in male patients with antidepressant-related erectile dysfunction (ED); in female patients, testosterone skin patches may increase the frequency of satisfactory sexual events. Combining higher doses of bupropion (300 mg/d) may also improve sexual function. Although it is generally believed that sexual adverse effects may disappear after discontinuation of SSRIs and SNRIs, this is not the case for some patients. At this point, psychological factors may play some role and need to be taken into account.
Sedation
Patients sometimes need the sedative effect of antidepressants, but in many cases this effect is problematic; the sedative effect of TCAs and mirtazapine is more pronounced, while SSRIs and SNRIs are relatively weak. For this side effect, first consider lowering the dose of the drug or taking it at bedtime; if this does not work, consider switching to a less sedating antidepressant, such as bupropion, SSRIs or SNRIs. for patients with excessive sleep and fatigue, a combination of modafinil may improve wakefulness.
While taking antidepressants, patients may also experience a decrease in motivation and emotional response levels, i.e., emotional retardation. This effect is dose-dependent, reversible, and occurs mainly in patients taking SSRIs. For this condition, lowering the drug dose or switching to another antidepressant such as bupropion may be helpful.
Discontinuation syndrome
The final hurdle that patients need to cross is the discontinuation syndrome. The incidence reported in studies varies widely, ranging from 5% to 86%, and occurs within 1-7 days of tapering or discontinuation of SSRIs or SNRIs. Typical symptoms are electrical shocks in the brain, visual flashes and headache, while other symptoms include dizziness, depression, insomnia, fatigue, anxiety, agitation and nausea.
The incidence of this syndrome is related to the half-life of the SSRIs, and is significantly higher with paroxetine than with the other SSRIs. For some patients, the use of SSRIs with a longer half-life (e.g., fluoxetine) may be helpful in the process of discontinuing the drug. As in the following cases.
IV. Serious adverse reactions
In addition to those unpleasant and troubling adverse reactions, physicians should be aware of several serious adverse reactions to newer antidepressants. For example, suicidal ideation may occur in 4-14% of adolescent patients during the initiation of antidepressant treatment.
Even with only short-term application of SSRIs or venlafaxine, patients are at a mildly elevated risk of upper gastrointestinal bleeding compared with conventional TCAs, especially those at high risk, such as patients with alcohol abuse. Although depression is associated with metabolic syndrome and some antidepressants may induce weight loss, there may not be a relationship between the two. In young adults, long-term antidepressant use may increase the risk of type 2 diabetes.
Although TCAs are associated with a higher risk of cardiovascular adverse effects, convulsions, and granulocyte deficiency, these adverse effects may also occur in patients taking other antidepressants. The risk of adverse reactions can be minimized by developing a treatment strategy after identifying risk factors, carefully reviewing all appropriate antidepressants, considering patients’ personal preferences, and monitoring carefully.
V. Conclusion
When prescribing antidepressants, physicians will be faced with troublesome and sometimes quite serious adverse drug reactions. Before initiating antidepressant therapy, physicians should adequately inform patients about potential adverse drug reactions and encourage them to actively engage with their physicians to adequately address problems when they are identified. A basic principle is to choose a drug that is well tolerated by the patient, start at the lowest dose, and slowly increase the dose.
Medication tolerance and symptom relief are of equal concern during monitoring. It is important to distinguish adverse drug reactions from depressive symptoms, such as fatigue and carbohydrate cravings. Given that most adverse reactions are transient, observational waiting is often a reasonable option when they occur. Before changing medications, one can first try to lower the dose of the medication or adjust the duration of administration. If the above regimen is ineffective, (hyper-indication) combination of other drugs may be considered.