The patient was a 27-year old Caucasian male who had a difficult childhood with various mood, anxiety and cognitive symptoms including bipolar I disorder. He said he started drinking alcohol and smoking marijuana at age 18 to treat those symptoms. By 20-22 years old, he was using a wide range of substances, including dextromethorphan, ecstasy, methamphetamine, cocaine, opioids, MDMA, mescaline and opium.

Age 22, he had a severe manic episode with psychosis; he was involuntarily hospitalized for 5-6 weeks, then again a year later for 4 weeks. Since then he has taken many psychiatric medications, all of which were ineffective, partially effective or caused adverse effects. He has relapsed to substance abuse several times, both when taking psychiatric meds and without. Longest period of abstinence was 2 years.

Current diagnoses:
Bipolar I Disorder, most recent episode manic, severe with psychotic symptoms; cannabis abuse, early full remission; Polysubstance Dependence, Sustained Full Remission.

The patient’s current adverse effects included tremors, dry mouth, agitation, anger/rage reactions, daytime sedation, insomnia and nightmares. His depressed, irritable and unstable mood continued partially treated.

Most recent labs:
CBC, chemistry, lipids, T4 and TSH all within normal limits.

Current medications:
bupropion SR 150 mg BID, fluoxetine 20 mg qd, Invega 6 mg tab qd, lamotrigine 150 mg qd, gabapentin 600 mg 1 tab bid and 2 tab qhs, Strattera 100 mg qam, trazodone 100 mg 2-3 tab hs and prazosin 12 mg qhs.

Others: simvastatin, omega 3, niacin, milk thistle, vitamins B complex, B12 and D.

Evaluation:

• CYP2D6:          Intermediate metabolizer
• CYP2C9:          Normal metabolizer
• CYP2C19:        Rapid metabolizer

Wellbutrin’s active metabolite exposure may increase in CYP2D6 intermediate metabolizers and by inhibition (Prozac). Management: Monitor for tremors, anticholinergic effects and insomnia. When necessary, decrease the dose or prescribe desvenlafaxine, mirtazapine or Viibryd if appropriate.

Strattera exposure increased in CYP2D6 intermediate metabolizers and by inhibition (Prozac, bupropion). Management: Monitor for GI disturbances, insomnia, fatigue, cardiovascular changes and hepatotoxicity. When necessary, decrease the dose or prescribe an alternative such as methylphenidate or dexmethylphenidate.

After reviewing the results 4 of 8 current psychiatric meds were identified with potential major interactions among them: Strattera, Wellbutrin, Prozac and trazodone.

Tapered and discontinued all 4 and started Pristiq (SNRI may minimize serotonin activity, metabolized by 3A4). For middle sleep disruption, ruled out benzodiazepine-receptor meds and mirtazapine (may worsen nightmares).

No med for ADHD for now, may consider Intuniv or methylphenidate. Ruled out Adderall because he abused it and it caused severe adverse effects. The patient also spoke with his PCP, who discontinued simvastatin, started atorvastatin.

Conclusion:

The patient had a difficult transition the first 2 weeks, with increased irritability, “quick anger/rage flashes,” “dark and suicidal thoughts,” decreased concentration and increased distractibility.  At 4 weeks he was feeling better, mood more stable and less depressed, anger decreased, concentration improved, “not all over the place,” sleep ”so-so” but nightmares stopped. All previous adverse effects resolved; no tremors, no dry mouth, no agitation and no daytime sedation.

At 6 weeks, mood continued to improve, daytime energy increased moderately, and sleep was more restorative.

He said “sleep is getting back to normal without trazodone,” using melatonin 6-9 mg, and prazosin 12 mg effective for nightmares, “I don’t even remember my dreams anymore, which is nice.” Concentration improved but he asked to restart Strattera due to “rambling thoughts, hard to organize,” and decreased motivation and “drive.” He recently graduated from a vocational/technical college with a media certification.