Bipolar disorder is one of the leading causes of disability due to having a mental illness. A range of pharmacological and psychological interventions are effective in the management and prevention of acute episodes of bipolar disorder. However, these incur considerable costs, as well as productivity losses due to time off work. This topic presents the economic cost-effectiveness of pharmaceutical treatments.

What is the evidence for pharmaceutical costs?

Low quality evidence is unable to determine the cost-effectiveness of pharmaceutical treatments for bipolar disorder.

November 2021

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Mode of administration with reference to bipolar disorder usually refers to oral or injection administration. Studies have shown that people with bipolar disorder can relapse due to lack of adherence to prescribed medications. Long-acting injectable medications are a treatment option for those who are not adhering to, or do not remember to take, their prescribed oral preparations. This topic assesses whether injectable medications are more effective than placebo or oral preparations for treating symptoms of bipolar disorder.

What is the evidence for mode of administration for people with bipolar disorder?

High quality evidence suggests a small to medium-sized effect of fewer relapses with long-acting injection second generation antipsychotics than with placebo, with less all-cause treatment discontinuation.

Moderate to low quality evidence found no differences in relapse rates or all-cause discontinuation between long-acting injection second generation antipsychotics and oral antipsychotics or treatment as usual, although prolactin-related adverse events were found less often with long-acting injection second generation antipsychotics.

November 2021

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The placebo effect involves showing a response to non-active formulas in clinical trials. Non-active formulas are used as a control condition to establish whether the active formulas are more effective for symptoms than what would normally be observed simply due to expectations that the medications are effective. The medication being tested should result in greater improvements in symptoms than placebo if their active ingredients are doing what they are meant to do. The placebo response can include both improvements in symptoms as well as adverse reactions that have been associated with the medication being tested.

What is the evidence for placebo response?

Moderate quality evidence suggests greater response to active medications than to placebo for both mania and depression symptoms. This was found in both adults and children with bipolar disorder. Response rates to active medications was around 49% for mania and 52% for depression. Response rates to placebo was around 32% for mania and 39% for depression. Greater response to active medications for mania, but not for depression, was related to greater relative efficacy (comparing active medications to placebo). Greater response to placebo for mania, but not for depression, was related to decreased relative efficacy.

Moderate to low quality evidence suggests longer treatment duration increased the likelihood of placebo response for depression. Greater depression symptom severity at baseline (start of treatment) increased the likelihood of response to active treatment for depression. People with mania and psychotic symptoms, and people who completed the trials, were more likely to have active drug-associated improvements in mania symptoms. People with mixed-state diagnoses were less likely to have active drug-associated improvements in mania symptoms. Increased placebo response for mania was associated with older patients’ age, and female sex. Studies conducted in the USA or Europe (vs. other regions), and studies conducted over three or more regions (vs. fewer regions) were more likely to report greater placebo response.

November 2021

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Polypharmacy is combined pharmaceutical treatment that is used for patients who are unresponsive or partially responsive to single therapies.

What is the evidence for polypharmacy?

Moderate quality evidence finds fewer relapses with any combination therapy than with any monotherapy or placebo. The following combination therapies reduced overall relapse rates more than placebo for over 6 months (in descending order of effectiveness); aripiprazole + valproate, lithium + oxcarbazepine, lithium + valproate, and aripiprazole + lamotrigine.

Moderate to high quality evidence finds greater improvement in depression symptoms with combined olanzapine + fluoxetine therapy than with placebo, olanzapine or lamotrigine alone. Overall, adjunctive second-generation antidepressants were associated with a small improvement in depression in the short-term (< 12 weeks), however there was an increased risk of switching to mania/hypomania in the longer term (~52 weeks).

Moderate quality evidence finds a medium-sized reduction in relapses to any mood episode after 6 months of treatment with antipsychotics plus mood stabilisers (mostly lithium and valproate) compared to placebo plus mood stabilisers. Aripiprazole plus mood stabilisers and quetiapine plus mood stabilisers prevented both depression and mania relapses, while lurasidone plus mood stabilisers was more effective for preventing relapse to depression, and ziprasidone plus mood stabilisers was more effective for preventing relapse to mania.

Adding antipsychotics to mood stabilisers also resulted in greater response and remission compared to mood stabilisers alone, but was associated with more sleepiness, somnolence, weakness, faintness, dizzyness, appetite, weight gain, tremor, use of antiparkinsonian drugs, dry mouth and thirst, and changes in triglycerides, fasting glucose, and HbA1c levels. Compared to antipsychotics alone, adding mood stabilisers to antipsychotics improved mania but not depression and resulted in more tremor, sleepiness, and vomiting.

November 2021

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Achieving an optimum pharmacological response may require switching medications. Reasons for switching include individual differences in response, sensitivity to side effects, and peculiarities of bipolar disorder such as changes in mood over time.

What is the evidence for switching medications?

Moderate to low quality evidence suggests switching to lithium from quetiapine due to having had an affective event resulted in less time to recurrence of a mood episode (particularly depression) compared to patients who stayed on quetiapine. Switching to oral olanzapine from risperidone long-acting injections found time to recurrence of any mood episode was significantly longer with olanzapine, particularly for depressive episodes.

Low quality evidence is unable to determine any benefits of switching between other medications.

November 2021

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