Table 2.
Pharmacotherapy for the Treatment of Bipolar Disorder
| Drug | Dose | Advantages | Considerations | Monitoring |
|---|---|---|---|---|
| Aripiprazole | Start 5–15mg daily. Can increase by 5–10mg every two weeks. NTE 30 mg daily. | Low QTc prolongation risk, quick onset for mania, may lower prolactin, lower MetS risk, LAAI. | Long half-life, dose adjust for drug interactions (2D6, 3A4) | Akathisia, TD, weight gain, suicidal thoughts/behaviors |
| Asenapine | Start 5–10mg twice daily, NTE 20 mg. Transdermal: Start 3.8mg/24 hours, after 1 week may increase to 5.7mg/24 hours or 7.6mg/24 hours. |
SL/transdermal formulations, good option in gastric bypass or other diseases that affect GI absorption of drugs. | Potential metabolic side effects, orthostasis, induced by smoking (1A2), cost. | Weight gain, EPS, akathisia, TD, drowsiness, oral hypoesthesia, suicidal thoughts Topical: application site reactions/rash. |
| Carbamazepine | Start 100–200 mg once or twice daily, increase by 200 mg/day every 1–4 days. Target dose 800–1200mg/day. Effective dose may range 200–1800 mg/day. Requires dose adjustment 3–4 weeks after initiation due to autoinduction (3A4). |
Effective for comorbid seizures and trigeminal neuralgia. | HLA allele testing for those of Asian ancestry, SJS, hyponatremia, agranulocytosis, cardiac side effects, causes significant drug interactions. | Sodium, TFT, renal function, suicidal thoughts/behaviors. Therapeutic serum levels are not established for treating BP. Some target seizure disorder treatment levels, 4–12 mcg/mL. |
| Cariprazine | Mania: 1.5 mg on day one, 3 mg on day two, then increase by 1.5–3 mg every two weeks, usual dose range 3–6mg Depression: 1.5 mg for two weeks, increase to 3 mg based on efficacy and tolerability |
Lower risk metabolic side effects, may lower prolactin, low QTc prolongation risk. | Long half-life, initial dose titration orthostasis, dose adjust for drug interactions (3A4), cost. | EPS, akathisia, TD, insomnia, nausea, suicidal thoughts/behaviors. |
| Divalproex | Load dose: Initiate 25 mg/kg for three days, draw trough serum concentration on fourth day and adjust dose based on result. Fixed dose: initiate at 250–500mg daily and adjust based on tolerability. Usual maintenance dose for either dose initiation method: 15mg/kg/day. |
Numerous dosage forms, preferred in history of TBI, rapid onset when load dosed. | Avoid in women of child-bearing potential (teratogenic, PCOS). | Weight gain, sedation, suicidal thoughts/behaviors. Target serum concentration 50–125 mcg/mL (85–125 mcg/mL for ER formulation). |
| Haloperidol | Start 2–5 mg daily, titrate as tolerated. NTE 15mg. | Cost, LAAI. | Hyperprolactinemia, adjust for drug interactions (2D6, 3A4). | EPS, akathisia, TD. |
| Lamotrigine | 25 mg daily weeks 1 and 2, 50 mg daily weeks 3 and 4, 100 mg week 5, 200 mg week 6. Patients taking valproate: 25 mg every other day weeks 1 and 2, 25 mg daily weeks 3 and 4, 50 mg daily, Week 5 onwards, increase by 25–50 mg every 1–2 weeks. Max daily dose = 200 mg daily. In patients taking carbamazepine, phenytoin, phenobarbital or primidone: 50 mg daily weeks 1 and 2, 100 mg daily weeks 3 and 4, 200 mg daily week 5, 300 mg daily week 6, 400mg daily week 7. Patients may require 500mg daily. |
Benefits for depression, relatively well tolerated, low weight gain potential. | Delayed effect due to slow titration, SJS risk, class 1B antiarrhythmic. | Rash, drug interactions, suicidal thoughts/behaviors. |
| Lithium | Start 300 mg daily with dose adjustment every 5–7 days according to serum trough concentration, tolerability or symptoms. | Neuroprotective, decreased suicide risk, efficacy for mania and depression. | GI side effects, polyuria/polydipsia, diabetes insipidus, drug interactions. | Renal function, tremor, acne. Target serum concentration 0.6–0.8 mEq/L (0.8–1.2mEq/L in acute mania). |
| Lurasidone | Start 20 mg daily, increase by 20 mg weekly. NTE 120 mg/day. Doses >80 mg of limited benefit. | Quick onset for depression, lower risk of metabolic side effects. | Take with >350 kcal, dose adjust for Child-Pugh class B, C & CrCl<50mL/min, cost. | EPS, akathisia, TD, suicidal thoughts/behaviors. |
| Olanzapine | Start 5–15mg daily, may increase by 5 mg increments to a typical dose up to 20 mg. | Quick onset for mania. | Significant MetS, induced by cigarette smoking (1A2). | Sedation, weight gain, constipation, orthostatic hypotension, EPS, TD. |
| Paliperidone | 6mg daily, increase by 3 mg every 5 days, NTE 12 mg, most patients require >6mg. | Quick onset for mania, LAAI. | MetS, renal dose adjustment, hyperprolactinemia. | Weight, EPS, TD, renal function. |
| Quetiapine | Start 25–50 mg nightly. Increase dose by 50 mg weekly up to a maximum total daily dose of 800mg. Typical depression target dose = 200–300 mg daily. For quetiapine XR : 300mg on day 1, increase to 400-600mg on day 2; target dose of 400-800mg daily. | Quick onset, possibly anxiolytic, efficacy for mania and depression. | MetS, orthostatic hypotension, available as once daily formulation. | Weight gain, dizziness, sedation, constipation, TD, suicidal thoughts/behaviors. |
| Risperidone | Start 1–2mg daily or in 2 divided doses; can increase by 1 mg daily to a usual dose of 4mg per day. NTE 6mg. | Quick onset for mania, LAAI. | MetS, orthostasis and tachycardia, hyperprolactinemia, consider dose adjustment with renal impairment. | Weight gain, EPS, TD, headache, renal function. |
| Ziprasidone | Start 20–40 mg twice daily with meals, can increase dose on second day to typical dose of 40 mg-80 mg twice daily. | Low MetS. | Take with >/=500 calories, QTc prolongation. | EPS, akathisia, TD, dizziness, headache, drowsiness, suicidal thoughts/behaviors |
Abbreviations: EPS, extrapyramidal side effects; GI, gastrointestinal; LAAI, long acting antipsychotic injection; MetS, metabolic side effects; NTE, not to exceed; SJS, Stevens-Johnson Syndrome; TD, tardive dyskinesia; TFT, thyroid function tests.