Approaches to Preventing Relapse in Bipolar Disorder: Addressing Nonadherence and Prodromal Symptoms

Alan C. Swann, MD

Department of Psychiatry and Behavioral Sciences, University of Texas Medical School, Houston

Phases and Goals of Treatment

Bipolar disorder is a chronic and complex illness requiring lifelong treatment. Due to the episodic nature of the disorder, treatment for patients with bipolar disorder consists of 3 phases, each with specific strategies and goals.1 First, the treatment for an acute episode of bipolar disorder aims to help the patient achieve symptomatic recovery. Once symptom improvement occurs, treatment moves into the continuation phase, in which the medicines that helped the patient achieve stability are continued but adjustments (eg, to dosage or timing of doses) may be made to increase tolerability. Poorly tolerated medications or adjunctive medications deemed nonessential for the patient are gradually tapered; however, they may be reinstated or replaced with an alternative medicine should the patient experience the early signs of relapse.

The goal of the continuation phase is functional recovery, ie, when the patient can handle normal living and working conditions. During this phase, patients and clinicians should establish structured routines that will help the patient maintain long-term mood stability, such as taking medicines regularly, having regular physical and social activity, and maintaining a regular rhythm of sleep. Patients should be trained to monitor themselves for prodomal symptoms that might indicate impending relapse and should record routine activities, such as what type of exercise they perform each day or the number of hours they sleep each night, to help in recognizing trends that affect mood. Finally, clinicians should help patients develop a support network consisting of family, friends, support groups, and other therapists or physicians.

Upon reaching functional recovery, patients transition into the maintenance phase of treatment. The treatment goals of the maintenance phase are to prevent the recurrence of acute episodes and to optimize the adaptive functioning of the patient. Two crucial elements in preventing relapse during the maintenance phase are addressing nonadherence and managing subsyndromal or prodromal symptoms.

Pharmacologic Therapy and Nonadherence

Maintenance medicine strategies. Pharmacotherapy is the primary treatment for patients with bipolar disorder. The medicines that have been successful in helping the patient achieve syndromal and functional recovery should be continued during the maintenance phase. However, the clinician must continually re-evaluate all medications for effectiveness, appropriate dosage, and adverse effects. Evidence-based pharmacologic options for maintenance treatment include lithium, lamotrigine, divalproex, olanzapine, quetiapine, risperidone long-acting injection, and aripiprazole. Adjunctive therapies include quetiapine, risperidone long-acting injection, and ziprasidone.2

The usefulness of antidepressants in the maintenance treatment of bipolar disorder is less clear. Depressive symptoms dominate in bipolar disorder, but no controlled studies have shown antidepressants to be effective in reducing depressive relapse.3,4 However, a subset of patients who require antidepressants to achieve remission from an acute depressive episode seem to benefit from continued treatment with antidepressants and appear to lose benefit if antidepressant treatment is discontinued too soon after remission.5 Conversely, bipolar disorder is associated with treatment-resistant depression, particularly due to loss of antidepressant treatment response.6 Long-term treatment with antidepressants, in addition to possibly inducing mania or rapid cycling, may induce chronic irritable dysphoria in patients with bipolar disorder.7

Addressing nonadherence. One study8 found that almost half of patients hospitalized for bipolar disorder stopped taking their medicines within 2 years of discharge. Discontinuing medication increases a patient’s risk for relapse, and a rapid discontinuation is associated with a more rapid relapse.9 Therefore, clinicians need to encourage continuation of a successful treatment, and, if patients must discontinue a treatment, should taper the medicine slowly, if possible, to delay relapse and allow time for the introduction of a new medicine.

Patients often discontinue pharmacologic treatment on their own due to side effects. While some side effects, such as hair loss, acne, stomach upset, tremor, or sedation, are not physiologically dangerous, they may cause the patient enough discomfort, embarrassment, or disfigurement that they stop taking the medicine. Other potential side effects that may not be as noticeable to the patient actually pose greater risks to the patient’s health. For example, some medications can cause organ toxicity, insulin resistance, bone marrow suppression, or renal failure. Clinicians should monitor for these types of adverse events, which can progress gradually, and proactively address them. Weight gain, a common side effect of psychotropic drugs, is not only distressing to the patient but is physiologically dangerous and should be addressed proactively.

A study10 that examined why patients receiving lithium discontinued their medication found a low concordance between the responses of patients and their clinicians, indicating a lack of communication (AV 1AV 1). Further, the patients’ responses illustrated their difficulty accepting the chronic nature of bipolar disorder, indicating a need for greater education about the illness. Communication and education are vital so that clinicians understand their patients’ concerns and patients can be partners in treatment decisions.

Additional Maintenance Strategies to Prevent Relapse

Strategies that have proven helpful in preventing relapse and improving functionality for patients include using psychoeducation and adjunctive psychotherapies, helping patients detect signs of a recurrence, and facilitating patient and caregiver participation in support groups. Psychosocial treatments that were established during the acute and continuation phases should be continued as needed during the maintenance phase.

Psychoeducation and psychotherapy. Relatively structured psychosocial interventions (such as interpersonal social rhythm therapy, family-focused therapy, cognitive therapy, and group psychoeducation) used adjunctively with pharmacotherapy can reduce relapse rates11 and lower treatment costs12 compared with treatment as usual for patients with bipolar disorder. For example, group psychoeducation has been shown to reduce the number of patients who relapse, the number of recurrences per patient, and the number and length of hospitalizations per patient.13 Cognitive therapy can address specific issues such as social functioning, coping with prodromal symptoms, and dysfunctional thinking regarding goal attainment.14


Group psychoeducation for caregivers also has been shown to reduce recurrence in patients with bipolar disorder (AV 2AV 2).15 Caregivers’ beliefs about bipolar disorder can influence the amount of burden they associate with the patient’s illness independently of the severity of the patient’s symptoms,16 and a high level of caregiver burden can, in turn, adversely affect the patient’s clinical outcome.17 Psychoeducation may reduce the burden for caregivers by improving their attitude toward the illness and increasing the collaborative nature of treatment.

Addressing interepisode impairment. Even when euthymic, patients with bipolar disorder may have subtle neurocognitive impairment18 and problems with sustained attention that may interfere with processing efficiency.19 Approximately 70% of patients with bipolar disorder have a clinically significant sleep disturbance even when euthymic.20 Interepisode impulsivity is also increased in patients with bipolar disorder, especially in those who have a history of substance abuse.21 These impairments can be affected negatively by subsyndromal symptoms, stress, and substance abuse and should be treated with both pharmacologic and psychosocial treatments.

Anticipating an episode. Patients with bipolar disorder usually experience a prodromal period that may last for weeks or months before the onset of an affective episode.22 Changes that appear early in this prodromal period include changes in motivated activity, the sleep-activity cycle, impulsivity, or interpersonal behaviors. Affect changes, such as sadness or euphoria, usually occur later in the prodromal stage. Prodromal symptoms are typically consistent within individuals, and patients can learn to recognize their early prodromal symptoms and use behavioral strategies to help prevent relapse.23 Strategies that patients can use to avoid relapse include making small adjustments to their medication regimen, changing daily routines, reducing stress or overstimulation, and increasing social contact and support (AV 3AV 3).

Support groups. Advocacy groups for patients with major affective disorders can provide educational materials, wellness tools, and support for patients and their families or caregivers. One such group is the Depression and Bipolar Support Alliance (dbsalliance.org).


Mood stabilizers are necessary during all phases of treatment for bipolar disorder, and addressing nonadherence is critical for preventing relapse. Psychoeducation strategies for both patients and caregivers can help to prevent relapse for patients with bipolar disorder. Patients can take an active and responsible role in managing their illness through monitoring their symptoms to detect prodromal signs of relapse, protecting their daily rhythms and routines, and maintaining healthy activities.

For Clinical Use

  • Continue successful pharmacologic treatments during the maintenance phase to help prevent relapse while monitoring for adverse effects that can lead to treatment discontinuation or health problems
  • Use adjunctive psychotherapeutic interventions for patients and caregivers to improve attitudes toward the illness and encourage treatment adherence
  • Teach patients and caregivers to recognize, monitor, and address prodromal signs of a recurrence


aripiprazole (Abilify), divalproex (Depakote and others), lamotrigine (Lamictal and others), lithium (Lithobid and others), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone long-acting injection (Risperdal Consta), ziprasidone (Geodon)

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