Case debrief

The patient has a lengthy history of likely MDD with mixed features with clear iatrogenic exacerbation due to the stimulants and antidepressants

She has a clear history of attempting to take and use approved mood stabilizers, antipsychotics, and antidepressants with some ability to reach euthymia, but also at the cost of many adverse effects

Use of a BZ sedative and a non-approved wakefulness-promoting stimulant ultimately proved effective, but is also counterintuitive in a patient with a history of mixed features and psychosis

The clonazepam (Klonopin) was tolerated well and without metabolic issues, tremors, EPS, TD, or laboratory abnormalities. All these factors thwarted her previous care and ability to sustain euthymia

Modafinil (Provigil) had limited data in bipolar depression and could have been risky given her manic escalation and movement disorder on previous classic, high-dose amphetamine stimulants

Modafinil (Provigil) was judged to be theoretically safer as its mechanism of action is less robust with regard to DA facilitation than a classic stimulant, and its isomer armodafinil (Nuvigil) also has published successful trials for use in bipolar depression

Take-home points

This case emphasizes the need for obtaining information from previous providers to help delineate a complicated diagnosis and also determine what medications have been dosed in full therapeutic trials

Guidelines suggest using mood stabilizers and atypical antipsychotics to treat all phases of bipolar disorder or those with mixed features of any kind

Antidepressants and stimulants ideally should not be utilized in bipolar patients unless warranted and assuming that an adequate mood stabilizer or antipsychotic is therapeutically in place

Guidelines for monitoring end organ damage should be heeded and followed. This patient developed movement disorder and blood laboratory abnormalities that were discovered through usual monitoring practices

If patients are to be rechallenged on previously difficult-to-tolerate medications, adequate informed consent, increased follow-ups and monitoring should be considered. Slower titration schedules and perhaps slow-release preparations should be utilized

When approved medications fail to help or are intolerable, referring to guidelines and the available literature is warranted when prescribing off-label medications

In the absence of literature, consulting with colleagues, attending continuing medical education (CME) activities, or using theoretical mechanism of action, knowledge about off-label medications is warranted to help guide prescribing

• – Documentation in the medical record is needed regarding the clinical rationale of off-label use

Performance in practice: confessions of a psychopharmacologist

What could have been done better here?

• – Was it inappropriate to retry divalproex (Depakote), thiothixene (Navane), or lithium carbonate?

  • Patient developed the same side effects compared to previous trials

  • However, in the current trials, attempts were made to monitor, minimize, and treat side effects as they emerged

  • Patient also achieved documented therapeutic levels on all agents, and documented euthymia was noted despite the adverse effects

  • Ultimately however, the agents were not tolerated and forced clinical decisions to lean toward the use of off-label approaches

  • The myriad of records actually showed good tolerability for clonazepam but risk of dependence, relatively less evidence base, and taboo of using sedatives to treat mixed features likely interfered with the decision to believe in the collected chart information

Possible action items for improvement in practice

• – For diagnosis, in the absence of old records, consider using diagnostic rating scales such as the Mood Disorder Questionnaire (MDQ) or the Psychiatric Diagnostic Screening Questionnaire (PDSQ)

• – Consult peer-reviewed practice guidelines when making real-time treatment decisions in these complex cases

• – In the case of hypochondriacal, side effect-prone patients, sometimes believing the history is warranted and retrials may not be wise