Medication Management for a 22-Year-Old Woman with Anxiety, Paranoia, Insomnia, Fluoxetine Intolerance, and Cocaine Use History
Primary Recommendation
Discontinue quetiapine and switch to sertraline 50 mg daily as first-line treatment, combined with cognitive behavioral therapy for insomnia (CBT-I), while avoiding quetiapine due to its lack of FDA approval for anxiety/insomnia, significant metabolic risks even at low doses, and documented abuse potential in patients with substance use history. 1, 2, 3
Rationale for Discontinuing Quetiapine
Guideline-Based Contraindications
Quetiapine is explicitly not recommended for primary insomnia according to the American Academy of Sleep Medicine, which states that atypical antipsychotics like quetiapine "may only be suitable for patients with comorbid insomnia who may benefit from the primary action of these drugs" and warns of "significant side effects (e.g., neurological side effects, weight gain, and dysmetabolism)." 1
The insomnia guideline places quetiapine in the lowest tier of pharmacologic options—reserved only after failure of benzodiazepine receptor agonists, ramelteon, and sedating antidepressants—due to "insufficient evidence of efficacy for chronic primary insomnia" and "potential for significant side effects." 1
Critical Safety Concerns in This Patient
Documented abuse and dependence potential: Multiple case reports describe quetiapine abuse specifically among patients with substance use disorders, who use it intranasally, intravenously, or combined with cocaine to enhance sedation—making it particularly dangerous in a patient with cocaine abuse history. 4
Metabolic toxicity even at low doses: Studies demonstrate that quetiapine 25–200 mg daily (the typical "off-label" insomnia range) causes significant weight gain and triglyceride elevations across all psychiatric disorders, with one retrospective cohort showing "significant increases in weight compared to baseline" even at these low doses. 5, 6
Increased mortality and dementia risk in recent data: A 2025 study of older adults found low-dose quetiapine for insomnia was associated with 3.1-fold increased mortality (HR 3.1,95% CI 1.2–8.1), 8.1-fold increased dementia risk (HR 8.1,95% CI 4.1–15.8), and 2.8-fold increased fall risk (HR 2.8,95% CI 1.4–5.3) compared to trazodone. 7
Dose escalation risk: A 2017 case report documented a patient requiring dose escalation to 50 times the typical off-label dose (from 25–100 mg to 5000 mg) over two years due to tolerance, raising concerns about dependence. 8
Recommended Treatment Plan
Step 1: Initiate Sertraline as First-Line SSRI
Start sertraline 25 mg daily for 3–7 days (a "test dose" to minimize initial activation symptoms in this anxious patient), then increase to 50 mg daily. 2
Sertraline is the preferred SSRI because it has superior tolerability compared to fluoxetine (which caused irritation in this patient), lower discontinuation syndrome risk than paroxetine, and minimal drug interaction potential—critical given her substance use history. 2
Titrate sertraline in 50 mg increments every 1–2 weeks if response is inadequate, up to a maximum of 200 mg daily, allowing 6–8 weeks at therapeutic doses before declaring treatment failure. 2
Step 2: Implement Cognitive Behavioral Therapy for Insomnia (CBT-I)
CBT-I is the guideline-recommended first-line treatment for chronic insomnia, consisting of multicomponent therapy including cognitive therapy, stimulus control, sleep restriction, and relaxation therapy. 1
Pharmacotherapy should be supplemented with behavioral and cognitive therapies when possible, and "medication tapering and discontinuation are facilitated by CBT-I." 1
Sleep hygiene alone is insufficient and must be combined with other CBT-I components. 1
Step 3: If Insomnia Persists After 4–6 Weeks on Sertraline + CBT-I
Add a short-intermediate acting benzodiazepine receptor agonist (zolpidem, eszopiclone, zaleplon) or ramelteon as second-line pharmacotherapy, per the insomnia guideline's recommended sequence. 1
Alternatively, consider trazodone 25–100 mg at bedtime, which has "moderate efficacy for improving sleep quality and/or duration" and is listed as a sedating antidepressant option before atypical antipsychotics in the treatment algorithm. 1
Avoid restarting quetiapine given the guideline's explicit recommendation against off-label use for primary insomnia and the patient's substance abuse history. 1, 4
Addressing the Paranoia Component
When Paranoia Warrants Antipsychotic Treatment
If paranoid thoughts represent true psychotic symptoms (fixed false beliefs, perceptual disturbances) rather than anxiety-related hypervigilance, quetiapine may be appropriate at FDA-approved antipsychotic doses (150–800 mg daily), not the subtherapeutic doses used for sedation. 3
However, the clinical presentation suggests anxiety-related paranoia (worry about others' perceptions, hypervigilance) rather than psychosis, which should respond to SSRI treatment and CBT. 2
Monitor for emergence of true psychotic symptoms during sertraline treatment; if these develop, psychiatric consultation for appropriate antipsychotic dosing is warranted. 3
Critical Safety Monitoring
Suicidality Surveillance
All SSRIs carry FDA black-box warnings for treatment-emergent suicidal thinking in patients ≤24 years, with pooled absolute risk of 1% versus 0.2% with placebo (NNH = 143). 2
Conduct weekly assessments during the first month, especially in the first 1–2 weeks after starting sertraline or after any dose change. 2
Activation Symptoms
Monitor for motor restlessness, insomnia worsening, impulsivity, or agitation during the first 2–4 weeks, which are more common in younger patients and anxiety disorders. 2
If activation occurs, temporarily reduce the sertraline dose; symptoms typically resolve within days. 2
Substance Use Relapse
Screen for alcohol use disorder and monitor for cocaine relapse, as anxiety and insomnia are common triggers for substance use. 1
Sertraline has no abuse potential and does not interact with cocaine, making it safer than quetiapine in this population. 2, 4
Treatment Duration
Continue sertraline for a minimum of 4–9 months after satisfactory response for first-episode anxiety/depression. 2
Consider longer duration (≥1 year) if symptoms are recurrent or chronic. 2
Taper gradually when discontinuing to minimize discontinuation syndrome, though sertraline has lower risk than paroxetine. 2
Common Pitfalls to Avoid
Do not continue quetiapine simply because "it helps"—the short-term sedative benefit does not justify the metabolic risks, abuse potential, and lack of evidence for long-term efficacy in primary insomnia. 1, 7, 5
Do not switch SSRIs prematurely—allow 6–8 weeks at therapeutic sertraline doses before declaring treatment failure. 2
Do not prescribe benzodiazepines as first-line treatment—they are second-line after CBT-I and carry their own dependence risk in a patient with substance use history. 1
Do not ignore the substance use history—quetiapine's documented abuse potential in cocaine users makes it particularly dangerous in this patient. 4