What medication should be prescribed for a 41-year-old patient with a possible manic episode, unknown history of bipolar disorder, and a history of amphetamine use, who is currently taking Prozac (fluoxetine) and has a history of instability, suicidal attempt, and impulsive behavior?

Immediate Medication Management for Antidepressant-Induced Mania with Substance Use

Discontinue Prozac immediately and initiate a mood stabilizer—either lithium or valproate—as first-line treatment for this acute manic episode, while addressing the amphetamine use that is likely contributing to mood destabilization. 1

Critical First Steps

Discontinue the Antidepressant

• Stop Prozac (fluoxetine) immediately, as antidepressant monotherapy is a well-established trigger for manic episodes in bipolar disorder and can cause rapid cycling 1, 2
• Antidepressants without mood stabilizers carry significant risk of mood destabilization in patients with bipolar disorder 3
• The patient's manic symptoms following Prozac dose increase strongly suggests antidepressant-induced mania 2

Address Amphetamine Use

• The positive amphetamine screen is a critical confounding factor—amphetamines are known to induce manic symptoms and can precipitate mania in predisposed individuals 2
• Confront the discrepancy between her denial and positive lab results directly; verify through prescription drug monitoring program (PDMP) whether she has legitimate prescriptions 1
• Mood stabilization must be achieved before considering any stimulant medications, even if she has comorbid ADHD 1

First-Line Pharmacologic Treatment

Initiate a Mood Stabilizer Immediately

Option 1: Lithium (Preferred for Suicide Risk)

• Lithium is the strongest choice given her suicide attempt history, as it reduces suicide attempts 8.6-fold in patients with bipolar disorder 3
• Start lithium 300mg twice daily, titrate to therapeutic level (0.6-1.2 mEq/L) 4
• Obtain baseline labs: CBC, thyroid function, urinalysis, BUN, creatinine, serum calcium 3
• Monitor lithium levels, renal and thyroid function every 3-6 months 1
• Critical warning: Lithium requires careful third-person supervision due to lethality in overdose given her suicide attempt history 3

Option 2: Valproate (Preferred for Mixed/Dysphoric Features)

• Valproate shows higher response rates (53%) compared to lithium (38%) in mixed episodes 1
• Start valproate 250mg twice daily, titrate to therapeutic level (50-125 μg/mL) 4
• Obtain baseline labs: liver function tests, CBC, pregnancy test 1
• Monitor serum drug levels, hepatic function, and hematological indices every 3-6 months 1
• Allow 6-8 weeks at adequate doses before concluding inefficacy 1

Add an Atypical Antipsychotic for Severe Mania

For severe presentations with marked impulsivity and instability, combination therapy is first-line 1, 5

Recommended: Olanzapine or Quetiapine

• Olanzapine 10-15mg daily is FDA-approved for acute mania and has robust efficacy data 4
• Olanzapine combined with lithium or valproate is superior to mood stabilizer monotherapy 4
• Alternative: Quetiapine 300-600mg daily (start 50mg, titrate rapidly) 1
• Quetiapine plus valproate is more effective than valproate alone for acute mania 1

Monitor metabolic parameters closely:

• BMI monthly for 3 months, then quarterly 1
• Blood pressure, fasting glucose, and lipids at baseline, 3 months, then yearly 1
• Atypical antipsychotics carry significant weight gain risk, particularly olanzapine 6

Acute Symptom Management

For Agitation and Anxiety (PRN)

• Low-dose lorazepam 0.5-1mg PRN (maximum 2mg daily, not more than 2-3 times weekly) 1
• Avoid high-dose benzodiazepines when combined with antipsychotics due to excessive sedation 1
• Set clear limits on frequency to prevent tolerance and dependence 1

Safety and Monitoring Plan

Immediate Safety Measures

• Restrict access to lethal means: medications, firearms, other methods 3
• Involve family/caregivers in safety planning and medication supervision 3
• Assess suicidal ideation at every visit, particularly during medication changes 3
• Consider more frequent visits (weekly) during acute stabilization phase 3

Substance Use Monitoring

• Repeat urine drug screen in 1-2 weeks to verify abstinence from amphetamines 1
• If amphetamine use continues, mood stabilization will be extremely difficult to achieve 1
• Address substance use disorder with appropriate referrals once acute mania is controlled 1

Duration of Treatment

• Continue mood stabilizer for minimum 12-24 months after acute episode stabilizes 1, 3
• Many patients require lifelong treatment—over 90% of noncompliant patients relapse versus 37.5% of compliant patients 1
• Never discontinue lithium abruptly, as withdrawal increases suicide risk 7-fold and relapse risk dramatically within 6 months 3
• If atypical antipsychotic is used, continue for at least 12 months after remission begins 3

Critical Pitfalls to Avoid

• Never use antidepressants as monotherapy in bipolar disorder—this patient's presentation demonstrates exactly why 1, 3
• Do not restart Prozac even after mood stabilization; if depression recurs, use olanzapine-fluoxetine combination or add antidepressant only with established mood stabilizer 1
• Avoid premature discontinuation of mood stabilizers—inadequate treatment duration is a leading cause of relapse 1
• Do not ignore the amphetamine use—ongoing stimulant use will sabotage any mood stabilization attempt 2
• Ensure adequate trial duration (6-8 weeks) before concluding a medication is ineffective 1

Psychosocial Interventions

• Provide psychoeducation about bipolar disorder, medication adherence, and substance use 3
• Involve family in treatment planning to improve adherence and monitor for relapse 3
• Consider cognitive behavioral therapy once acute mania resolves 3
• Address medication adherence barriers, as over 50% of bipolar patients are nonadherent 6