A Game Plan for Prevention of Antidepressant Adverse Effects


Recommendations from an international panel of experts on the management of MDD.



Highly individualized assessment and monitoring are crucial to prevention of adverse outcomes in patients who receive antidepressant medication, according to a recent international consensus statement.1 Contributors to the consensus include experts in the management of MDD from the Australasian Society for Bipolar and Depressive Disorders, Canadian Network for Mood and Anxiety Treatments, World Federation of Societies of Biological Psychiatry, and International Society for Affective Disorders.

Adverse effects of antidepressants
Common adverse effects of antidepressant medications include headache, nausea, agitation, sedation, sexual dysfunction, cognitive changes, weight gain, and metabolic abnormalities. Rarer, more serious adverse events include cardiac, neurologic, and hepatic effects. Possible increased risk of suicidality is also an issue in certain patient populations.

The panel offered guidance to ameliorate adverse events and optimize treatment. They emphasized the importance of the diagnostic work-up, which should be completed before a diagnosis or treatment decision is made.

Diagnostic work-up
The baseline assessment should include details about the nature and course of the disorder, the patient’s clinical history, differential diagnoses, medical and psychiatric comorbidities, and information on prior treatment response and tolerability as well as treatment response to psychiatric medications of any family members. Tools may include self-rated questionnaires and symptom scales in addition to a thorough diagnostic interview.

Whereas views diverge among experts regarding the routine use of baseline laboratory testing, tests to rule out physiologic conditions that can mimic or arise with MDD symptoms are recommended. Included are a complete blood cell count to rule out anemia, thyroid function testing, alcohol and substance abuse screening, infectious disease screening, 24-hour urinary free cortisol testing to rule out hyper- or hypocortisolemia, and neuroimaging and neuropsychological testing to rule out cognitive impairment. The panel noted that fatigue and anhedonia caused by viral infections can overlap with or be mistaken for depression as can hyper- or hypocortisolemia, small vessel disease, and incipient dementia.

Baseline tests to assess how a patient may react to an antidepressant include body mass measurements, evaluation of sexual health, cardiologic parameters (eg, blood pressure and ECG readings), pregnancy status, liver function, and bone density. Certain antidepressants may affect weight and, in turn, morbidities such as metabolic syndrome. Antidepressant medications also can affect sexual function or, more commonly, compound existing problems with sexual function, and SSRIs in particular can affect bone density.

Treatment selection
Treatment selection should be based on the efficacy and tolerability of individual antidepressants, the patient’s history of response and tolerance and clinical symptom profile, and whether the patient belongs to a special population (eg, juvenile, elderly, pregnant, dealing with comorbidities) as well as the patient’s personal preferences and cost constraints. Furthermore, whether to treat pharmacologically should be thoroughly discussed with the patient, and the decision should be aligned with patient preferences. The full range of options, including psychosocial treatments, should be discussed.

Once the patient has initiated treatment, periodic monitoring of weight changes, liver function, and blood and cardiovascular parameters is recommended. Clinicians should especially be vigilant for hyponatremia in patients, particularly women and the elderly, who are receiving selective serotonin or norepinephrine reuptake inhibitors. Vigilance is strongly recommended for indices of metabolic syndrome, sexual dysfunction, and suicidality. Evaluation, which may include symptom scale use, should be conducted at each scheduled patient visit.

The panel also advised that the treating physician must be ready to make an immediate decision when an adverse reaction occurs. Should treatment be discontinued, modified, or continued? Clinicians are urged to discuss all adverse reactions with the patient and arrive at treatment decisions through mutual agreement.

The bottom line
Because antidepressant treatment can be associated with risks, careful assessment and monitoring are required, the panel concluded. Adverse events can be minimized by following safety monitoring recommendations and by meticulous attention to the individual patient’s needs and risk factors.


1. Dodd S, Mitchell PB, Bauer M, et al. Monitoring for antidepressant-associated adverse events in the treatment of patients with major depressive disorder: an international consensus statement.World J Biol Psychiatry. 2017 Oct 6:1-19. [Epub ahead of print]

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