Treating bipolar disorder can be difficult. Medication is the first-line treatment, but even with medication people still experience symptoms and 40%-60% experience relapse within two years. Because of this, it’s vital for patients to be prescribed the most effective medication for them. What is more effective for one person may not be as effective for another. That is why there are hundreds of possible medication combinations to treat bipolar disorder. Since combination therapy is common, it’s important to evaluate how medications work together to treat bipolar disorder. A new study looks at combination therapy including lurasidone (Latuda) with either lithium or valproate (Depakote) noting the combination’s effectiveness as maintenance therapy.

Lurasidone is an atypical antipsychotic approved for the treatment of schizophrenia and bipolar depression. It has previously only been indicated for treatment of acute depression in bipolar disorder. It works by reducing the effects of both dopamine and serotonin at certain places in the brain. Common side effects include: agitation, anxiety, diarrhea; dizziness, drowsiness, fatigue, light-headedness, nausea, restlessness, stomach upset, vomiting and weight gain.

Lithium is a salt compound that works as a mood stabilizer. It inhibits excitatory neurotransmitters like dopamine and glutamate. It also increases GABA, which can in turn reduce anxiety. Blood tests must be performed regularly to check for the concentration of lithium in the blood. If levels are too high, it can cause toxicity which can affect thyroid and kidney function. Common side effects include: confusion, feeling faint, irregular heartbeat, difficulty breathing, muscle stiffness, tiredness or weakness, weight gain, frequent urination and increased thirst.

Valproate is a mood stabilizer. It is also an anticonvulsant and can be used to prevent migraines. It works by regulating voltage-dependent sodium channels, which cause excitability in the brain and it also increases GABA, much like lithium. Common side effects include: change in appetite, constipation, diarrhea, dizziness, drowsiness, hair loss, headache, indigestion, nausea, stomach cramps or pain, trouble sleeping, vomiting, weakness and weight changes.

Because the drugs work in different ways, combining them has the potential to make a more effective treatment. However, this has to be tested. A new study, led by Joseph R. Calabrese of University Hospitals Case Medical Center, Case Western Reserve University in Cleveland, Ohio, sought to see if lurasidone could be used effectively and safely as maintenance therapy in combination with either lithium or valproate when compared to placebo.

The study followed 496 patients for 28 weeks, observing reactions to up to 80mg/day of lurasidone or placebo combined with either lithium or valproate. During the study the participants were either considered stable or experiencing mild depressive symptoms. Here is what they found:

  • The probability of relapse during the study was 21% for those taking lurasidone versus 52% taking placebo.
  • For non-rapid cycling patients, reduction of risk of relapse was 31%.
  • Lurasidone was significantly more effective at lengthening time between episodes (either depressive, manic or hypomanic) than placebo.
  • Combining lurasidone with valproate was slightly more effective at lengthening time between episodes than combining lurasidone with lithium.
  • 5% of people taking lurasidone experienced at least one “severe” side effect, compared to 4% taking placebo. The most common side effects reported were nausea and drowsiness.
  • During the double-blind phase, average weight gain with lurasidone was 0.2kg compared to 0.0kg with placebo.
  • There was no difference between lurasidone and placebo regarding changes in cholesterol, triglycerides, glucose or HbA1c.
  • Minimal changes in prolactin levels were seen with combination therapy.
  • The most effective dose of lurasidone was between 80-120mg/day.
  • Lurasidone was more effective at preventing depressive episodes than manic episodes when used as maintenance therapy.

When combined with either lithium or valproate there was a significant decrease in the probability of an oncoming episode and it showed minimal side effects. Lurasidone as combination therapy appears to be a safe and effective long-term treatment for bipolar disorder.

 

 

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