People with bipolar disorder may relapse with manic, mixed, or depressive episodes, regardless of what their previous episode involved. The chance of relapse is complicated by differential response to treatments and other factors associated with the disorder. Preventing the development of rapid cycling symptoms is particularly paramount to good outcomes.

What is the evidence for relapse in people with bipolar disorder?

Moderate to high quality evidence suggests there were more major life events occurring just prior to a mood episode than prior to an euthymic, stable phase of the disorder, indicating transitions and major life changes may trigger a mood episode.

Moderate quality evidence suggests the risk of any subsequent mood episode after any first mood episode is around 44% in the first year, reducing to around 20% in the second and third years. Adolescents show consistent rates of relapse over three years of around 20%. The median time to any subsequent mood episode after any first mood episode is around 1.5 years. This time is longer in people with bipolar I than bipolar II disorder, in adolescents than adults, in people tested in an euthymic than in a mood phase, and in people with ongoing subclinical symptoms. Children and adolescents with bipolar disorder were more likely to be readmitted to a psychiatric hospital than children and adolescents with other psychiatric disorders.

Moderate to low quality evidence suggests a small effect of greater risk of any subsequent mood episode after a first episode of depression than after a first episode of mania or mixed symptoms. The risk of a depressive subsequent mood episode was higher in people with bipolar II than bipolar I disorder. However, the polarity of the index episode generally predicted the polarity of the subsequent episode.

For people with a first episode of mania, moderate quality evidence suggests rates of relapse are around 26% by 6 months, and up to 48% by 4 years. Older age at first-episode of mania was associated with lower relapse rates. For people with a first episode of mania or mixed symptoms, moderate to low quality evidence suggests rates of relapse are around 35% by 12 months up to 58% by 4 years.

For pregnant women, there is moderate to low quality evidence showing the median rate of mood episodes during pregnancy is around 24%, with most episodes being depressive. For women in the postpartum period, mood relapse rates are around 37%, which is similar to psychotic relapse rates in women with a history of postpartum psychosis, however severe relapses are greater in women with a history of postpartum psychosis. Women taking prophylactic medications during pregnancy or during the postpartum period had fewer relapses than women who were medication free during pregnancy.

November 2021

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Bipolar disorder is a disabling condition characterised by episodes of mania or hypomania and depression. Adherence to pharmacological treatment is critical for effective control of symptoms and to prevent relapse.

What is the evidence for pharmaceutical treatments for relapse prevention?

Overall, moderate to high quality evidence finds maintaining antipsychotic or mood stabiliser treatment is associated with fewer relapses than discontinuing antipsychotic or mood stabiliser treatment.

Medications compared to placebo

Moderate quality evidence finds the following medications reduced overall relapse rates more than placebo (in descending order of effectiveness); asenapine, aripiprazole + valproate, lithium + oxcarbazepine, olanzapine, aripiprazole once monthly, lithium + valproate, quetiapine, aripiprazole + lamotrigine, aripiprazole, lithium, valproate, risperidone long-acting injectable, and lamotrigine. Carbamazepine and paliperidone performed no better than placebo.

Compared to placebo plus mood stabilisers, there were fewer relapses after six months of treatment with second-generation antipsychotics plus mood stabilisers (mostly lithium or valproate). Aripiprazole + mood stabilisers and quetiapine + mood stabilisers prevented both depression and mania relapses, while lurasidone + mood stabilisers was more effective for preventing relapse to depression, and ziprasidone + mood stabilisers was more effective for preventing relapse to mania.

For side effects, moderate to low quality evidence finds placebo was better tolerated than carbamazepine, lithium, or lithium + valproate. There was greater incidence of prolactin-related adverse events with long-acting injectable risperidone, more weight gain with olanzapine, risperidone, quetiapine and aripiprazole, more tremor with aripiprazole and risperidone, more restlessness with aripiprazole, and more sedation with olanzapine and quetiapine.

Medications compared to other medications

There were fewer relapses with olanzapine than with imipramine, paliperidone, or lamotrigine; fewer relapses with quetiapine than with imipramine or lamotrigine; fewer relapses with lithium or lithium + valproate than with imipramine; and fewer relapses with aripiprazole + valproate than with imipramine or paliperidone. There were fewer relapses, particularly to mania, with long-acting injectable risperidone or flupenthixol decanoate than with any oral medication.

For side effects, moderate to low quality evidence finds lamotrigine was better tolerated than carbamazepine, lithium, or lithium + valproate. Long-acting injectable risperidone was associated with more prolactin-related adverse events than any oral medications.

November 2021

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Studies have shown that about 80% of patients relapse to psychosis within 5 years of initial diagnosis. Antipsychotic drugs have played a central role in the treatment of schizophrenia for more than 50 years and antipsychotic use significantly reduces the risk of relapse.

What is the evidence for relapse prevention?

High quality evidence shows a small benefit of specialist first-episode psychosis programs (involving both psychosocial and pharmaceutical treatments) for reducing the risk of relapse and less all-cause discontinuation of treatment compared to treatment as usual. These programs may also reduce the length of hospital stay should relapse occur.

Moderate to high quality evidence suggests a medium-sized effect of reduced risk of relapse in people receiving antipsychotics, particularly clozapine, although antipsychotics resulted in more weight gain, movement disorders and sedation than placebo. Long-acting injectable antipsychotics may be more effective than oral antipsychotics, second-generation antipsychotics may be more effective than first-generation antipsychotics, and continuous antipsychotic use may be more effective than intermittent antipsychotic use.

Moderate quality evidence suggests a small to medium-sized effect of reduced risk of relapse in people receiving standard dose antipsychotics compared to people receiving very low dose antipsychotics (< 50% of daily defined dose), although standard dose antipsychotics resulted in more people dropping out of trials due to side effects. No differences were reported in relapses or side effects when low dose (50 to < 100% of daily defined dose) was compared to standard dose.

Moderate quality evidence suggests relapse and rehospitalisation rates were higher after discontinuation of antipsychotics in people in remission following a first-episode of psychosis. Relapse rates were highest in studies with a short follow-up (<1 year), a non-targeted or non-intermittent discontinuation strategy, a lower relapse threshold, a smaller sample size, and in samples of patients with drug or alcohol dependency.

October 2020

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Psychotic relapse is the reoccurrence of previously treated psychotic symptoms.  Effective early recognition may offer the potential for early intervention to prevent relapse, such as medication adjustment, psychosocial treatments, social support and stress reduction. Early warning signs are subjective experiences, thoughts and behaviours that occur immediately prior to a psychotic relapse, which signal to the patient or their family that their condition is deteriorating. It is important that these early signs be identifiable by family members or carers, as patients may minimise or disguise these symptoms in order to appear healthy or to avoid hospital readmission. The ability of patients to properly recognise altered experiences may also deteriorate as the symptoms progress and insight diminishes.

What is the evidence for psychotic relapse?

Moderate quality evidence suggests the rates of relapse following a first-episode of psychosis are around 28% at one year post-treatment and up to 54% at three years post-treatment. The relapse rate following discontinuation of antipsychotics in people with chronic schizophrenia is around 38%. Children and adolescents with a psychotic disorder were more likely to be readmitted to a psychiatric hospital than children and adolescents with other psychiatric disorders.

Most patients and family members could identify changes in experience or behaviour that preceded a psychotic relapse, and over 50% of patients reported a duration greater than one month between onset of warning signs and relapse. Common early warning signs include hallucinations, suspiciousness, change in sleep, anxiety, cognitive inefficiency, hostility, somatic symptoms, delusions, thought disorder, inappropriate behaviour, and depression.

Higher risk of relapse was associated with substance use disorders, poor medication adherence, high levels of critical family comments and expressed emotion, poor premorbid adjustment, high ambient temperature, and being in a perimenstrual phase for women. Factors most consistently associated with lower risk of relapse after discontinuation of antipsychotics include being maintained on a low antipsychotic dose prior to discontinuation, a shorter duration of untreated psychosis in the early stages of the disorder, better social functioning, and fewer previous relapses.

February 2022

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