What is the best course of treatment for a patient with bipolar disorder who is unstable on Kaplyta (dapagliflozin) and has previously tried every selective serotonin reuptake inhibitor (SSRI), experiencing severe manic episodes?

From the Guidelines

For a patient with bipolar disorder who is unstable on Kaplyta (dapagliflozin) and has previously tried every selective serotonin reuptake inhibitor (SSRI), experiencing severe manic episodes, I strongly recommend transitioning to a traditional mood stabilizer such as lithium or valproate, combined with an atypical antipsychotic medication, as the primary treatment approach. This recommendation is based on the treatment guidelines for bipolar disorder, which suggest that traditional mood stabilizers and/or atypical antipsychotic medications are the primary treatment for acute mania 1. The patient's history of trying every SSRI and continuing to experience severe manic episodes suggests that these medications are not effective for their condition, and may even be triggering or worsening their manic episodes. Key considerations for the treatment approach include:

• Starting with a mood stabilizer such as lithium (600-1200 mg/day) or valproate (750-1500 mg/day) to help control manic symptoms
• Adding a second-generation antipsychotic like quetiapine (300-800 mg/day) or olanzapine (5-20 mg/day) to enhance symptom control
• Gradually tapering off Kaplyta to minimize withdrawal effects and prevent symptom exacerbation
• Monitoring blood levels for lithium (target 0.6-1.2 mEq/L) or valproate (target 50-125 μg/mL) to ensure therapeutic levels
• Assessing the patient for adherence issues, substance use, and psychosocial stressors that might be contributing to treatment resistance
• Encouraging regular sleep patterns, stress management, and psychotherapy (particularly cognitive behavioral therapy or interpersonal and social rhythm therapy) as important adjuncts to medication.

From the FDA Drug Label

1.2 Bipolar I Disorder (Manic or Mixed Episodes)

Monotherapy — Oral ZYPREXA is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder Efficacy was established in three clinical trials in adult patients with manic or mixed episodes of bipolar I disorder: two 3- to 4-week trials and one monotherapy maintenance trial.

The best course of treatment for a patient with bipolar disorder who is unstable on Kaplyta (dapagliflozin) and has previously tried every selective serotonin reuptake inhibitor (SSRI), experiencing severe manic episodes, may be monotherapy with olanzapine (ZYPREXA), as it is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder.

• Key considerations:
  • The patient's instability on Kaplyta (dapagliflozin) and previous trials of SSRIs
  • The severity of the manic episodes
  • The potential benefits and risks of olanzapine treatment, including weight gain and dyslipidemia 2

From the Research

Treatment Options for Bipolar Disorder

The treatment of bipolar disorder, especially in patients who are unstable on their current medication and have a history of severe manic episodes, requires careful consideration of various factors, including the patient's response to previous treatments and their medical history.

• For patients with bipolar disorder who have tried every selective serotonin reuptake inhibitor (SSRI) and are experiencing severe manic episodes, combination therapy with mood stabilizers such as lithium, valproate, or lamotrigine may be effective 3.
• Lithium has been shown to have more evidence of efficacy than any other agent in preventing episodes of mania and depression, and it may be a better treatment choice for patients with a positive family history for bipolar disorder, mania-depression-interval pattern, few previous affective episodes/hospitalizations, high risk for suicide, and no comorbidities 4.
• Valproate may be more effective as an antimanic rather than prophylactic agent and might be a better choice for patients with many previous affective episodes/hospitalizations and psychiatric comorbidities 4.
• Atypical antipsychotic agents, such as quetiapine, aripiprazole, asenapine, lurasidone, and cariprazine, are also recommended for the treatment of bipolar disorder, but some are associated with weight gain 5.
• Olanzapine has been shown to be effective in preventing manic relapse, but its effectiveness in preventing depressive episodes is less clear 6.
• For the treatment of bipolar depression, olanzapine/fluoxetine combination, quetiapine, and lurasidone are approved medication treatments, but they differ in terms of tolerability 7.

Considerations for Treatment

When selecting a treatment for a patient with bipolar disorder, it is essential to consider the potential benefits and risks of each medication, including the risk of weight gain, metabolic syndrome, and other adverse events.

• The metric of the likelihood to be helped or harmed (LHH) can be used to illustrate the tradeoffs inherent in selecting medications 7.
• Individualizing treatment decisions will require consideration of the different potential adverse events that are more likely to occur with each medication 7.
• Early diagnosis and treatment are associated with a more favorable prognosis, and long-term treatment consists of mood stabilizers, such as lithium, valproate, and lamotrigine 5.