What are the long-term effects of selective serotonin reuptake inhibitor (SSRI) therapy in an adult woman with polycystic ovary syndrome (PCOS) and a history of anxiety and/or depression?

Long-Term Effects of SSRI Therapy for Anxiety and Depression

For long-term SSRI use in anxiety and depression, continue treatment for 4-9 months after achieving satisfactory response for a first episode, with even longer duration (potentially indefinite) for patients with recurrent episodes, while monitoring for common side effects like sexual dysfunction, weight changes, and gastrointestinal symptoms, as well as serious risks including bleeding, hyponatremia, and withdrawal symptoms upon discontinuation. 1

Treatment Duration and Maintenance

• After achieving response, continue SSRI therapy for 4-9 months minimum for first-episode depression to prevent relapse. 1
• For patients with two or more depressive episodes, significantly longer or indefinite maintenance therapy is beneficial to prevent recurrence. 1
• The distinction matters: relapse occurs during acute/continuation phases (same episode), while recurrence represents a new distinct episode during maintenance phase. 1

Common Long-Term Side Effects

Approximately 63% of patients on SSRIs experience at least one adverse effect during treatment: 1

• Sexual dysfunction, weight gain, and gastrointestinal symptoms (diarrhea, nausea) are the most persistent long-term effects. 1
• Dry mouth, headache, fatigue, tremor, insomnia, dizziness, and increased sweating commonly persist throughout treatment. 1, 2
• Nausea and vomiting are the most common reasons for discontinuation, though these typically emerge early in treatment. 1

Serious Long-Term Risks Requiring Monitoring

Bleeding Risk

• SSRIs increase gastrointestinal bleeding risk (OR 1.2-1.5), with substantially higher risk when combined with NSAIDs or antiplatelet agents. 1, 3
• Risk ranges from minor ecchymoses to life-threatening hemorrhage. 3

Metabolic and Electrolyte Effects

• Hyponatremia occurs in 0.5-12% of older adults on SSRIs, typically within the first month of treatment. 1
• Weight changes (both gain and loss) can occur, though average weight loss is minimal (1-2 pounds). 3

Cardiovascular Considerations

• QT prolongation is dose-dependent; citalopram carries FDA warnings not to exceed 40 mg/day (20 mg/day in adults >60 years). 1
• Escitalopram has lower QT prolongation risk compared to other SSRIs. 2

Hepatotoxicity

• 0.5-3% develop asymptomatic mild transaminase elevations, typically within six months. 1

Discontinuation Syndrome

Abrupt cessation causes withdrawal symptoms including dysphoric mood, irritability, dizziness, sensory disturbances (electric shock sensations), anxiety, confusion, and insomnia. 3

• These symptoms are generally self-limiting but can be serious. 3
• Gradual dose reduction is mandatory when discontinuing; if intolerable symptoms occur, resume the previous dose and taper more slowly. 3

Suicidality Monitoring

• SSRIs carry increased risk of suicidal thinking/behavior in patients up to age 24 years (absolute risk 1% vs 0.2% placebo; NNH=143). 1, 2
• Risk is highest in the first month of treatment and following dose adjustments. 1
• In adults over 65 years, SSRIs appear protective against suicidal behavior (OR 0.06). 1

Behavioral Activation

• Motor restlessness, insomnia, impulsiveness, disinhibited behavior, and aggression can occur, particularly early in treatment or with dose increases. 1, 2
• More common in younger patients and those with anxiety disorders versus depression. 1

Special Considerations for PCOS Context

While the expanded question mentions PCOS, the evidence shows: 4, 5, 6

• Women with PCOS have 3.78 times increased odds of depressive symptoms and 5.62 times increased odds of anxiety symptoms. 6
• Lifestyle modifications and cognitive behavioral therapy show the most promise for reducing depression/anxiety in PCOS patients, with conflicting data on psychiatric medications. 4
• SSRIs remain appropriate first-line pharmacotherapy when indicated, with no specific contraindications in PCOS. 7

Monitoring Protocol

• Begin monitoring within 1-2 weeks of initiation, focusing on suicidality, behavioral activation, and tolerability. 1
• Assess response at 6-8 weeks; modify treatment if inadequate response. 1
• Escitalopram demonstrates better tolerability than sertraline with lower gastrointestinal effects and fewer drug interactions due to minimal CYP450 effects. 2

Drug Interaction Considerations

• Combining SSRIs with other serotonergic medications (including certain analgesics) can cause serotonin syndrome. 1
• Serotonin syndrome occurs in 14-16% of SSRI overdoses, presenting with tremor, diarrhea, delirium, neuromuscular rigidity, and hyperthermia. 1