How to manage a 23-year-old with mixed mania and depression, history of gender dysphoria on testosterone (T) 75mg every 14 days, and prescribed Seroquel (quetiapine) 50mg for bipolar disorder, but is non-adherent to medication and exhibits impulsive spending?

Management of Non-Adherent 23-Year-Old with Mixed Mania/Depression, Gender Dysphoria on Testosterone

The immediate priority is addressing medication non-adherence by increasing quetiapine to a therapeutic dose (300-800mg/day for bipolar disorder) while simultaneously adding a mood stabilizer (lithium or valproate) given the severity of mixed episodes and treatment resistance indicated by non-adherence. 1, 2

Immediate Medication Optimization

Quetiapine 50mg is a subtherapeutic dose for bipolar disorder and explains the lack of efficacy and subsequent non-adherence. 3, 4

• The FDA-approved dosing for bipolar mania starts at 100mg on day 1, titrating to 400mg by day 4, with a target range of 400-800mg/day for acute mania 3
• For mixed episodes specifically, quetiapine monotherapy at 300-800mg/day has demonstrated efficacy in reducing both manic and depressive symptoms 5, 4
• The current 50mg dose is essentially a placebo dose—this patient has never received adequate treatment 3

Combination Therapy Strategy

Given the mixed episode presentation with impulsive spending (indicating manic features) alongside depression, combination therapy is superior to monotherapy. 1

• Add lithium or valproate as the foundational mood stabilizer while optimizing quetiapine dosing 1, 2
• Quetiapine plus valproate is more effective than valproate alone for mixed episodes in young adults 1
• The American Academy of Child and Adolescent Psychiatry recommends combination therapy with a mood stabilizer plus atypical antipsychotic for severe presentations and mixed episodes 1

Addressing Non-Adherence

Non-adherence in this case is likely multifactorial: subtherapeutic dosing leading to lack of efficacy, possible side effects at even low doses, and gender identity factors affecting treatment engagement. 6

• Men with bipolar disorder show lower self-perceived masculinity than population norms, and gender identity significantly affects adherence patterns 6
• For transgender individuals on testosterone, concerns about medication interactions and effects on gender-affirming treatment may contribute to non-adherence 7
• Directly address the patient's reasons for non-adherence before assuming treatment failure 6

Specific Interventions for Adherence:

• Psychoeducation about the inadequate dose previously prescribed and expected benefits at therapeutic dosing 1, 2
• Reassurance that quetiapine and mood stabilizers do not interfere with testosterone therapy 7
• Discussion of metabolic monitoring given testosterone's effects and quetiapine's metabolic risks 3
• Consider once-daily dosing at bedtime to improve adherence and utilize sedating properties 3

Testosterone Considerations

Testosterone 75mg every 14 days is within the typical range for gender-affirming hormone therapy and should be continued without interruption. 7

• There are no contraindications to combining testosterone with quetiapine or mood stabilizers 7
• Testosterone can affect mood, but discontinuation would cause significant gender dysphoria and worsen overall mental health 7
• Monitor for potential mood destabilization, though testosterone itself is not contraindicated in bipolar disorder 7

Titration Protocol

Start quetiapine 100mg at bedtime on day 1, increase to 200mg day 2, 300mg day 3, then 400mg day 4, with target of 400-600mg/day for mixed episodes. 3

• Simultaneously initiate lithium 300mg twice daily or valproate 250mg twice daily, titrating to therapeutic levels over 1-2 weeks 1, 2
• For lithium: target level 0.8-1.2 mEq/L; for valproate: target level 50-125 mcg/mL 1
• Baseline labs before starting mood stabilizer: CBC, comprehensive metabolic panel, thyroid function, pregnancy test, lipid panel, fasting glucose 1, 2

Monitoring Requirements

Comprehensive metabolic monitoring is essential given the combination of testosterone, quetiapine, and mood stabilizers. 3

• Baseline: BMI, waist circumference, blood pressure, fasting glucose, lipid panel, liver function, renal function, thyroid function 1, 3
• Follow-up: BMI monthly for 3 months then quarterly; blood pressure, glucose, lipids at 3 months then yearly 1
• Mood stabilizer levels and organ function every 3-6 months 1, 2
• Weight gain is common with quetiapine (occurs in most patients) and requires proactive dietary counseling 3

Management of Impulsive Spending

Impulsive spending indicates inadequately controlled manic symptoms requiring immediate mood stabilization. 1

• This symptom should improve with therapeutic dosing of quetiapine plus mood stabilizer within 1-2 weeks 1, 4
• Consider short-term benzodiazepines (lorazepam 0.5-1mg PRN, max 2-3 times weekly) for acute agitation while titrating medications 1
• Psychoeducation with family/support system about financial safeguards during acute episodes 1

Treatment Duration

Maintenance therapy must continue for minimum 12-24 months after stabilization, with many patients requiring lifelong treatment. 1, 2

• More than 90% of young adults with bipolar disorder who discontinue maintenance therapy relapse, compared to 37.5% who remain adherent 1
• Withdrawal of lithium specifically increases relapse risk 8-fold within 6 months 1
• Never discontinue maintenance therapy prematurely—this is the most common treatment failure 1

Psychosocial Interventions

Pharmacotherapy alone is insufficient; psychoeducation and cognitive-behavioral therapy significantly improve outcomes. 1, 2

• Provide education about bipolar disorder, medication effects, early warning signs of episodes 1, 2
• Address gender dysphoria-related stressors that may exacerbate mood instability 7, 6
• Family psychoeducation to improve medication supervision and reduce access to means for impulsive behaviors 1

Critical Pitfalls to Avoid

• Never use antidepressant monotherapy in mixed episodes—this will trigger mania or rapid cycling 1, 2, 3
• Do not accept 50mg quetiapine as adequate treatment—this dose has no evidence for bipolar disorder 3, 4
• Do not discontinue testosterone to "simplify" the regimen—this will worsen gender dysphoria and overall mental health 7
• Do not overlook metabolic monitoring—quetiapine causes significant weight gain and metabolic syndrome risk 3
• Do not assume non-adherence equals treatment refusal—inadequate dosing and lack of education are likely culprits 6