What to Do When Your Depressed Patient Develops Mania

It is not uncommon for a manic patient to report “depression” as the chief complaint or to omit elements related to psychomotor acceleration (such as racing thoughts or psychomotor agitation) in the description of symptoms. An accurate diagnosis often requires clinical probing and clarification of symptoms (eg, differentiating simple insomnia with consequent next-day fatigue from loss of the need for sleep with intact or even enhanced next-day energy) or discriminating racing thoughts from anxious ruminations that might be more intrusive than rapid.

Presentations of frank mania also can come to light as a consequence of symptoms, rather than as symptoms per se (eg, conflict in relationships, problems at work, financial reversals).

Particularly in patients who do not have a history of mania, avoid the temptation to begin or modify existing pharmacotherapy until you have performed a basic initial evaluation. Immediate considerations for initial assessment and management include the following:

Provide containment. Ensure a safe setting, level of care, and frequency of monitoring. Evaluate suicide risk (particularly when mixed features are present), and risk of withdrawal from any psychoactive substances.

Engage significant others. Close family members can provide essential history, particularly when a patient’s insight about her illness and need for treatment are impaired. Family members and significant others also often play important roles in helping to restrict access to finances, fostering medication adherence, preventing access to weapons in the home, and sharing information with providers about substance use or high-risk behavior.

Systematically assess for DSM-5 symptoms of mania and depression. DSM-5 modified criteria for mania/hypomania to necessitate increased energy, in addition to change in mood, to make a syndromal diagnosis. Useful during a clinical interview is the popular mnemonic DIGFAST to aid recognition of core mania symptoms:

• Distractibility
• Indiscretion/impulsivity
• Grandiosity
• Flight of ideas
• Activity increase
• Sleep deficit
• Talkativeness.

These symptoms should represent a departure from normal baseline characteristics; it often is helpful to ask a significant other or collateral historian how the
present symptoms differ from the patient’s usual state.

Assess for unstable medical conditions or toxicity states. When evaluating an acute change in mental status, toxicology screening is relatively standard and the absence of illicit substances should seldom, if ever, be taken for granted—especially because occult substance use can lead to identification of false-positive BD “cases.”¹

Stop any antidepressant. During a manic episode, continuing antidepressant medication serves no purpose other than to contribute to or exacerbate mania symptoms. Nonetheless, observational studies demonstrate that approximately 15% of syndromally manic patients continue to receive an antidepressant, often when a clinician perceives more severe depression during mania, multiple prior depressive episodes,current anxiety, or rapid cycling.²

Importantly, antidepressants have been shown to harm, rather than alleviate, presentations that involve a mixed state, and have no demonstrated value in preventing post-manic depression.³ Mere elimination of an antidepressant might ease symptoms during a manic or mixed episode.⁴

In some cases, it might be advisable to taper, not abruptly stop, a short halflife serotonergic antidepressant, even in the setting of mania, to minimize the potential for aggravating autonomic dysregulation that can result from antidepressant discontinuation effects.

Begin anti-manic pharmacotherapy. Initiation of an anti-manic mood stabilizer, such as lithium and divalproex, has been standard in the treatment of acute mania.

In the 1990s, protocols for oral loading of divalproex (20 to 30 mg/kg/d) gained popularity for achieving more rapid symptom improvement than might occur with lithium. In the current era, atypical antipsychotics have all but replaced mood stabilizers as an initial intervention to contain mania symptoms quickly (and with less risk than firstgeneration antipsychotics for acute adverse motor effects from so-called rapid neuroleptization).

Because atypical antipsychotics often rapidly subdue mania, psychosis, and agitation, regardless of the underlying process, many practitioners might feel more comfortable initiating them than a mood stabilizer when the diagnosis is ambiguous or provisional, although their longer-term efficacy and safety, relative to traditional mood stabilizers, remains contested. Considerations for choosing from among feasible anti-manic pharmacotherapies are summarized in Table 1.

Normalize the sleep-wake cycle. Chronobiological and circadian variables, such as irregular sleep patterns, are thought to contribute to the pathophysiology of affective switch in BD. Behavioral and pharmacotherapeutic efforts to impose a normal sleep-wake schedule are considered fundamental to stabilizing acute mania.

Facilitate next steps after acute stabilization. For inpatients, this might involve step-down to a partial hospitalization or intensive outpatient program, alongside taking steps to ensure continued treatment adherence and minimize relapse.

What Medical and Neurologic Workup is Appropriate?

Not every first lifetime presentation of mania requires extensive medical and neurologic workup, particularly among patients who have a history of depression and those whose presentation neatly fits the demographic and clinical profile of newly emergent BD. Basic assessment should determine whether any new medication has been started that could plausibly contribute to abnormal mental status (Table 2).

Nevertheless, evaluation of almost all first presentations of mania should include:

• Urine toxicology screen
• Complete blood count
• Comprehensive metabolic panel
• Thyroid-stimulating hormone assay
• Serum vitamin B12 level assay
• Serum folic acid level assay
• Rapid plasma reagin test.

Clinical features that usually lead a clinician to pursue a more detailed medical and neurologic evaluation of first-episode mania include:

• Onset age > 40
• Absence of a family history of mood disorder
• Symptoms arising during a major medical illness
• Multiple medications
• Suspicion of a degenerative or hereditary neurologic disorder
• Altered state of consciousness
• Signs of cortical or diffuse subcortical dysfunction (eg, cognitive deficits, motor deficits, tremor)
• Abnormal vital signs.

Depending on the presentation, additional testing might include:

• Tests of HIV antibody, immune autoantibodies, and Lyme disease antibody
• Heavy metal screening (when suggested by environmental exposure)
• Lumbar puncture (eg, in a setting of manic delirium or suspected central nervous system infection or paraneoplastic syndrome)
• Neuroimaging (note: MRI provides better visualization than CT of white matter pathology and small vessel cerebrovascular disease) electroencephalography.

Making An Overarching Diagnosis: Is Mania Always Bipolar Disorder?

Mania is considered a manifestation of BD when symptoms cannot be attributed to another psychiatric condition, another underlying medical or neurologic condition, or a toxic-metabolic state (Tables 3 and 4). Classification of mania that occurs soon after antidepressant exposure in patients without a known history of BD continues to be the subject of debate, varying in its conceptualization across editions of DSM.

The National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder, or STEP-BD, observed a fairly low (approximately 10%) incidence of switch from depression to mania when an antidepressant is added to a mood stabilizer; the study authors concluded that much of what is presumed to be antidepressant-induced mania might simply be the natural course of illness.¹⁰

Notably, several reports suggest that antidepressants might pose a greater risk of mood destabilization in people with BD I than with either BD II or other suspected variants on the bipolar spectrum.