Antidepressant Side Effects and How to Manage Them

A concise review of conventional and CAM approaches.

Posted Sep 27, 2019

Over 80 percent of individuals who take antidepressants experience at least one side effect such as drowsiness, headaches, rashes, blurred vision, weight loss, and disorders of sexual function. Side effects can significantly interfere with quality of life and frequently lead to stopping an antidepressant or reducing the dose to a level that is minimally effective or ineffective.

In fact, unpleasant side effects—not lack of effectiveness—is the most frequently cited reason for discontinuing an antidepressant. Surveys have found that physicians underestimate the frequency of side effects resulting in poor communication with patients about their concerns and delays in addressing side effects. This post is offered as an overview of common antidepressant side effects and effective conventional and complementary and alternative medicine (CAM) strategies for managing them.

Antidepressant side effects are difficult to distinguish from symptoms of depressed mood

It is often difficult to distinguish antidepressant side effects from symptoms of depression. For example, sleep problems, apathy, impaired concentration, constipation, dry mouth, dizziness and other somatic complaints are frequently reported by depressed individuals when not taking antidepressant medications. This situation is complicated by unpleasant sensations, anxiety or changes in cognition, that may occur after an antidepressant is discontinued, so-called ‘discontinuation syndromes.’ Abrupt discontinuation of venlafaxine and antidepressants in the same family (i.e. serotonin-norepinephrine reuptake inhibitors SNRI) may result in uncomfortable somatic sensations, insomnia, acute anxiety and agitation. When taking a SNRI antidepressant it is important to discuss not only side effects to taking the medication but adverse effects that may take place if the medication is abruptly discontinued.

The most common antidepressant side effects 

The most commonly reported side effects to antidepressants are dry mouth, drowsiness, and sexual dysfunction. Side effects considered to be most bothersome are weight gain, drowsiness and sexual dysfunction. Severe daytime sleepiness is the side effect that is most likely to result in early discontinuation of an antidepressant increasing risk of worsening in mood. Some side effects persist for the duration of treatment while others are transient and tend to diminish after the first weeks or months on an antidepressant. For example, sexual dysfunction, insomnia and drowsiness often last for several months. In contrast, nausea may resolve in days or weeks. Weight gain is seldom reported in the first weeks on antidepressant therapy but often emerges during the course of treatment, the so-called ‘metabolic syndrome’ sometimes resulting in pre-diabetes or other medical problems. 

Effective strategies for managing antidepressant side effects

Effective strategies for managing antidepressant side effects include selecting a medication least likely to cause bothersome side effects, taking the lowest dose that is effective, and using adjunctive medications or natural supplements to mitigate side effects when they occur. Below I briefly summarize conventional and CAM approaches for managing antidepressant side effects.

Sexual side effects usually occur soon after starting antidepressants and (above) generally persist throughout treatment. Over 50 percent of individuals who take antidepressants experience problems with sexual functioning including delayed or absent orgasm, reduced arousal and reduced libido. Among antidepressants paroxetine (Paxil™) has the highest rate of sexual side effects while buproprion and nefazodone have the lowest rates. Strategies for reducing sexual side effects include medications aimed at increasing libido and sexual dysfunction (e.g. sildenafil), timing sexual activity many hours after taking an antidepressant, taking drug ‘holidays,’ and taking medications that may restore normal sexual functioning such as buproprion and yohimbine. Herbals that may lessen the severity of sexual dysfunction caused by antidepressants include Ginkgo biloba, Panax ginseng, and Lepidium meyenii (maca root). These herbals are generally safe in combination with antidepressants and other psychotropic medications that affect serotonin or other neurotransmitters. Before taking an herbal in combination with an antidepressant it is prudent to consult with your psychiatrist or family doctor to ensure that the combination is safe.

Fatigue is a common side effect of antidepressants. The simplest approach to managing severe daytime drowsiness or fatigue is switching to nighttime dosing. Other effective approaches include dividing the dose into two separate doses or switching to a slow-release preparation (typically less sedating than instant release forms). If nighttime dosing is not appropriate or has been tried and failed, some individuals benefit from taking an ‘activating’ medication such as modafinil, or an activating supplement such as S-adenosylmethionine (SAMe). SAMe is generally safe when used adjunctively with antidepressants and is a reasonable choice since it has established antidepressant effects.

Gastrointestinal side effects including nausea, diarrhea and constipation are commonly reported by individuals taking antidepressants. Nausea can be addressed by taking an antidepressant with food, dividing the dose into two separate doses, or by switching to a controlled release preparation. Ginger is sometimes effective for reducing nausea. Over-the-counter antihistamines sometimes help to lessen nausea. Some individuals experience diarrhea in response to SSRI antidepressants, which may last for weeks or longer after starting treatment. There is evidence that probiotic drinks and psyllium may reduce diarrhea. Effective approaches to constipation include drinking more fluids, increasing fiber in the diet, and if needed, using an over-the-counter stool softener.

Weight gain can be both a symptom of depressed mood and a side effect of antidepressants. When a side effect of an antidepressant, weight gain is not dose-dependent, i.e. the amount of weight gained is independent of  the dose that is taken of the medication. Hence, it is of little benefit to reduce medication dosages in an attempt to reduce weight gain. A more effective strategy is switching to an antidepressant with a lower rate of weight gain. Mirtazepine is the antidepressant with the highest rate of weight gain, followed by the SSRIs (e.g. fluoxetine and sertraline) and the SNRIs venlafaxine and duloxetine. The antidepressants nefazodone, reboxetine and buproprion are associated with the lowest incidence of weight gain. The mood stabilizing drug topiramate is sometimes effective in reducing weight gain caused by antidepressants. Making changes in the diet and increasing physical activity are often helpful for reducing weight. Many natural supplements are marketed for weight gain however most are supported by equivocal research findings. 

Insomnia may occur in up to 25 percent of individuals who take antidepressants, and frequently persists for months resulting in unresolved daytime drowsiness and diminished quality of life. Insomnia is more frequently reported by individuals who take SSRIs than mirtazapine, trazodone, and nefazodone. Reboxetine has an even higher rate of insomnia than SSRIs. Beneficial approaches to insomnia include cognitive and behavioral approaches aimed at relaxation, improved sleep hygiene, reducing caffeine intake, taking an over-the-counter sleep aid or a sedating natural supplement such as melatonin and sedating herbal formulas containing extracts of valerian, passionflower, chamomile and lemon balm.

Collaborative care results in better and more proactive management of antidepressant side effects

I recently posted two short pieces on the advantages of collaborative care models that include evidence-based CAM. Collaborative care models have been established to result in improved outcomes for both medical and mental health problems. Research findings support that individuals seen for depressed mood who are managed by a team of medical and behavioral health specialists (i.e. in outpatient collaborative care clinic settings) receive greater and more proactive attention for complaints of antidepressant side effects, and these concerns are addressed more promptly and more effectively.

Bottom line

Side effects are the most commonly cited reasons for discontinuing antidepressants resulting in treatment failure and worsening of depressed mood. Effective strategies for reducing the incidence of antidepressant side effects include judicious selection by physicians and psychiatrists of an antidepressant taking into consideration each person’s unique history of side effects to previous antidepressant trials, keeping in mind important differences in antidepressant side effect profiles, and following conservative prescribing guidelines aimed at achieving the minimal effective dosage of the antidepressant that will most likely to be tolerable. Many conventional treatments and CAM therapies can be used to lessen the severity of antidepressant side effects. 


Kelly K, Posternak M, Alpert JE. (2008) Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues Clin Neurosci. 2008;10(4):409-18.

Hudson TJ1, Fortney JC, Pyne JM, Lu L, Mittal D. (2015) Reduction of patient-reported antidepressant side effects, by type of collaborative care. Psychiatr Serv. 2015 Mar 1;66(3):272-8.