What are the common side effects of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs)?

Common Side Effects of Antidepressants

The most common side effects of antidepressants include constipation, diarrhea, dizziness, headache, insomnia, nausea, sexual dysfunction, and somnolence, with approximately 63% of patients experiencing at least one adverse effect during treatment. 1, 2

General Side Effect Profiles by Antidepressant Class

SSRIs (Selective Serotonin Reuptake Inhibitors)

• Gastrointestinal effects: nausea, vomiting, diarrhea (sertraline has higher rates of diarrhea than other antidepressants) 1
• Sexual dysfunction: decreased libido, delayed orgasm, anorgasmia (particularly problematic with paroxetine) 1
• Sleep disturbances: insomnia or somnolence 1
• Headache and dizziness 1
• Risk of gastrointestinal bleeding (OR = 1.2 to 1.5), especially when combined with NSAIDs or antiplatelet medications 1
• Hyponatremia (0.5% to 12% in older adults), typically within the first month of treatment 1

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Higher incidence of nausea and vomiting compared to SSRIs (particularly with venlafaxine) 1, 2
• Increased blood pressure (especially with venlafaxine) 1
• Sexual dysfunction similar to SSRIs 1
• Potential for cardiovascular events with venlafaxine 1, 2
• Sweating and dry mouth 1

TCAs (Tricyclic Antidepressants)

• Anticholinergic effects: dry mouth, constipation, urinary retention, blurred vision 3
• Cardiac conduction abnormalities and QT prolongation 1
• Orthostatic hypotension 3
• Higher risk of hepatotoxicity compared to SSRIs 1
• Sexual dysfunction 1
• Sedation and weight gain 3

MAOIs (Monoamine Oxidase Inhibitors)

• Dietary restrictions to prevent hypertensive crisis 4
• Risk of serotonin syndrome when combined with other serotonergic medications 1
• Orthostatic hypotension 3
• Insomnia 3
• Sexual dysfunction 3

Serious Adverse Effects

Suicidality

• Slightly increased risk of suicidal ideation in adults 18-24 years (OR = 2.30) 1
• Neutral effect for adults 25-64 years 1
• Protective effect for adults 65 years and older (OR = 0.06) 1
• Risk typically appears within 1-2 months of initiation or dose increase 1
• SSRIs associated with increased risk for nonfatal suicide attempts compared to placebo (OR = 2.25) 1

Serotonin Syndrome

• Can occur within 24-48 hours after combining serotonergic medications 1
• Symptoms include mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity 1
• Particularly dangerous when MAOIs are combined with other serotonergic medications 1
• Can be fatal in severe cases 1

Other Severe Effects

• QT prolongation (particularly with citalopram, escitalopram, and amitriptyline) 1
• Seizures (higher risk with bupropion) 1, 2
• Hepatotoxicity (higher risk with nefazodone) 1, 2
• Risk of overdose (particularly dangerous with TCAs) 3

Medication-Specific Side Effects

Medication Comparisons

• Bupropion has significantly lower rates of sexual dysfunction compared to SSRIs 1, 2
• Paroxetine has higher rates of sexual dysfunction than other SSRIs 1
• Mirtazapine and paroxetine cause more weight gain than sertraline, trazodone, or venlafaxine 1, 2
• Trazodone causes more somnolence than bupropion, fluoxetine, mirtazapine, paroxetine, or venlafaxine 1
• Mirtazapine has a faster onset of action than fluoxetine, paroxetine, or sertraline 1

Special Populations

Older Adults

• Preferred agents include citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, and bupropion 1
• Paroxetine and fluoxetine should generally be avoided due to higher rates of adverse effects 1, 2
• Higher risk of hyponatremia (0.5-12%) compared to younger adults 1

Pregnancy and Breastfeeding

• Neonatal complications possible with third-trimester exposure (respiratory distress, feeding difficulties, irritability) 5, 6
• Potential risk of persistent pulmonary hypertension of the newborn with SSRI use after 20 weeks gestation 1, 5
• Paroxetine and sertraline are preferred during breastfeeding as they transfer in lower concentrations to breast milk 1
• Fluoxetine and venlafaxine produce the highest infant plasma concentrations during breastfeeding 1

Management of Side Effects

Sexual Dysfunction

• Consider switching to bupropion which has lower rates of sexual side effects 1, 2
• Sexual dysfunction often underreported but affects approximately 40% of patients 1, 7
• Usually begins within the first week of treatment 1

Gastrointestinal Effects

• Nausea and vomiting are the most common reasons for discontinuation 1
• Taking medication with food may help reduce GI symptoms 7
• Consider switching to an antidepressant with lower GI side effect profile if symptoms persist 2

Drug Interactions

• Carefully check for interactions with other serotonergic medications to prevent serotonin syndrome 1, 2
• Increased bleeding risk when SSRIs are combined with antiplatelet drugs or NSAIDs 1
• Warfarin effects may be altered when combined with SSRIs or SNRIs 5

Clinical Recommendations

• When initiating treatment, start at low doses and titrate slowly to minimize side effects, particularly in younger children and older adults 1, 2
• Monitor closely for suicidality, especially in the first months of treatment and following dose adjustments 1
• Educate patients about potential side effects before starting treatment to improve adherence 7
• Regular follow-up is essential as only 40% of patients report side effects to their prescribing physicians 7
• For patients with severe depression, the benefits of antidepressants typically outweigh the risks of side effects 1