What is the approach for a medicated bipolar patient who wants to discontinue their medication, currently taking a mood stabilizer (e.g. lithium or valproate) and an antipsychotic or antidepressant?

Approach to Medication Discontinuation in Bipolar Disorder

Direct Recommendation

A medicated bipolar patient on a mood stabilizer and antipsychotic who wishes to discontinue medication should be strongly counseled against discontinuation, as withdrawal of maintenance therapy is associated with relapse rates exceeding 90% in noncompliant patients versus 37.5% in compliant patients, and if discontinuation is pursued despite counseling, implement a gradual taper over months with intensive monitoring rather than abrupt cessation. 1, 2, 3

Critical Evidence Against Discontinuation

The risk of relapse is extraordinarily high and occurs rapidly:

• Withdrawal of maintenance lithium therapy increases relapse risk dramatically, especially within the first 6 months following discontinuation 2, 3
• More than 90% of adolescents who were noncompliant with lithium treatment relapsed, compared to only 37.5% of those who were compliant 2, 3
• The greatest risk of relapse occurs in the first 8-12 weeks after discontinuing medication 2
• Bipolar disorder is a recurrent illness requiring lifelong treatment in most cases, with some individuals needing indefinite therapy when benefits outweigh risks 1, 2

If Discontinuation Must Proceed: Structured Algorithm

Step 1: Comprehensive Pre-Discontinuation Assessment

Before discontinuing any medication, obtain detailed history: 1

• Review all previous psychiatric symptoms and their severity
• Document response to current and past medications through medical records
• Contact previous prescribers for collateral history
• Assess current symptom stability duration (minimum 12-24 months symptom-free recommended) 2, 3
• Evaluate suicide risk factors and history 2
• Identify environmental stressors, substance use, and medication adherence patterns 4

Critical contraindications to discontinuation:

• History of severe manic episodes with psychosis 3
• Recent mood instability (within past 12-24 months) 2, 3
• Multiple prior relapses after medication discontinuation 2
• Active suicidal ideation or recent suicide attempts 2
• Lack of adequate social support or monitoring capacity 3

Step 2: Determine Which Medication to Discontinue First

There are little to no data suggesting which medication to remove first in patients taking multiple medications 1, however, a rational clinical approach prioritizes:

1. Consider discontinuing the antipsychotic before the mood stabilizer if the patient has been stable, as mood stabilizers (lithium, valproate) show superior evidence for long-term relapse prevention 2, 5
2. Never discontinue both medications simultaneously 1
3. Lithium demonstrates superior anti-suicide effects (8.6-fold reduction in suicide attempts, 9-fold reduction in completed suicides) independent of mood-stabilizing properties, making it the last medication to consider discontinuing 2

Step 3: Implement Gradual Tapering Protocol

Prescribers are generally encouraged to taper medication slowly to avoid: 1

• Withdrawal symptoms (particularly with benzodiazepines if used adjunctively)
• Rebound worsening of symptoms (antipsychotics for agitation, lithium for mania) 1
• Unexpected return of symptoms weeks to months after the last dose 1

Specific tapering approach:

• Reduce dose by 25% every 4-8 weeks minimum (slower than typical antidepressant tapers) 1
• For lithium: taper over 3-6 months minimum given high relapse risk with rapid discontinuation 2, 3
• For valproate: similar gradual reduction over months 5
• For atypical antipsychotics: reduce by 25% every 4-6 weeks 1

Step 4: Intensive Monitoring Plan

Develop a comprehensive monitoring strategy before initiating taper: 1

• Weekly visits during initial taper phase to assess for early warning signs 3
• Monthly visits for 6-12 months after complete discontinuation 2
• Close follow-up for at least 2-3 months after stopping medication, as this is the highest risk period for relapse 2

At each visit, systematically assess: 2

• Mood symptoms (both manic and depressive features)
• Sleep patterns and quality
• Irritability, impulsivity, and judgment
• Suicidal ideation
• Medication adherence to remaining agents
• Substance use
• Environmental stressors
• Early warning signs of relapse

Patients with mood and anxiety disorders may have medication tapered only to have a return of symptoms weeks to months after their last dose, requiring extended monitoring periods 1

Step 5: Establish Clear Relapse Prevention Plan

Before discontinuation, establish written criteria for medication reinitiation: 3

• Specific symptoms that trigger immediate medication restart
• Emergency contact numbers and crisis plan
• Family/caregiver education about early warning signs 3
• Agreement for immediate psychiatric evaluation if symptoms emerge 3

Common Pitfalls to Avoid

Critical errors that increase morbidity and mortality:

• Premature discharge or discontinuation before adequate stabilization (minimum 12-24 months symptom-free) 2, 3
• Inadequate duration of monitoring after discontinuation (must continue for months, not weeks) 1, 2
• Discontinuing medications in outpatient settings with short follow-up intervals, which may result in unmonitored return of symptoms 1
• Failure to involve family/caregivers in monitoring plan, missing early warning signs 3
• Abrupt cessation rather than gradual taper, dramatically increasing relapse risk 1
• Insufficient attention to medication adherence issues during the discontinuation trial 3

Psychosocial Interventions to Maximize Success

If discontinuation proceeds, mandatory adjunctive interventions include: 2, 3

• Psychoeducation about symptoms, course of illness, high relapse risk, and importance of monitoring 2, 3
• Cognitive-behavioral therapy to identify early warning signs and develop coping strategies 2
• Family-focused therapy emphasizing early symptom recognition and crisis intervention 3
• Regular sleep hygiene and circadian rhythm maintenance 4
• Avoidance of environmental triggers (seasonal light changes, shift work, circadian disruption) 4

Special Considerations by Medication Class

For mood stabilizers (lithium, valproate):

• Lithium withdrawal carries the highest relapse risk and should be tapered most slowly 2, 3
• Valproate discontinuation requires monitoring for seizure risk if used at high doses 5
• Both require continued laboratory monitoring during taper (renal/thyroid for lithium, hepatic for valproate) 2

For atypical antipsychotics:

• May be discontinued before mood stabilizers if patient has been stable 2
• Monitor for withdrawal dyskinesia or rebound psychosis 1
• Continue metabolic monitoring during taper 2

Final Clinical Caveat

The evidence overwhelmingly supports indefinite maintenance therapy rather than discontinuation 2, 3, 5, 4, 6. Maintenance therapy should continue for at least 12-24 months after the acute episode, with many individuals requiring lifelong treatment 2, 3. The combination of high relapse rates (>90% in noncompliant patients), reduced life expectancy (12-14 years shorter), elevated suicide risk (annual rate 0.9% vs 0.014% in general population), and 15-20% lifetime suicide completion rate makes discontinuation a high-risk decision that should only proceed with full informed consent and intensive monitoring 4, 6.