Treating bipolar mania in the outpatient setting: Risk vs reward

Obtaining pretreatment blood work can help a clinician determine whether a medication is safe to prescribe and establish causality if laboratory abnormalities arise after treatment begins. Ideally, the psychia­trist should follow consensus guidelines developed by the International Society for Bipolar Disorders⁴ or the American Psychiatric Association (APA)⁵ and order appropriate laboratory tests before prescrib­ing anti-manic medications. Determine the pregnancy status of female patients of child-bearing age before prescribing a potentially teratogenic medication, especially because mania is associated with increased libido.⁶

Manic patients might be too disorga­nized to follow up with recommendations for laboratory testing, or could wait sev­eral days before completing blood work. Although not ideal, to avoid delaying treat­ment, a clinician might need to prescribe medication at the initial office visit, without pretreatment laboratory results. When the patient is more organized, complete the blood work. Keeping home pregnancy tests in the office can help rule out pregnancy before prescribing medication.

Medication. Meta-analyses have estab­lished the efficacy of mood stabilizers and antipsychotics for treating mania,^7,8 and sev­eral consensus guidelines have incorporated these findings into treatment algorithms.⁹

For a patient already taking medications recommended by the guidelines, assess treatment adherence during the initial inter­view by questioning the patient and family. When the logistics of phlebotomy permit, obtaining the blood level of psychotropics can show the presence of any detectable drug concentration, which demonstrates that the patient has taken the medication recently.

If there is no evidence of nonadherence, an initial step might be to increase the dos­age of the antipsychotic or mood stabilizer that the patient is already taking, ensuring that the dosage is optimized based on FDA indications and clinical trials data. The rec­ommended rate of dosage adjustments dif­fers among medications; however, optimal dosing should be reached quickly because a World Federation of Societies of Biological Psychiatry task force recommends that a mania treatment trial not exceed 2 weeks.¹⁰

Dosage increases can be made at weekly visits or sooner, based on treatment response and tolerability. If there is no ben­efit after optimizing the dosage, the next step would be to add a mood stabilizer to a second-generation antipsychotic (SGA), or vice versa to promote additive or syn­ergistic medication effects.¹¹ Switching one medication for the other should be avoided unless there are tolerability concerns.

For a patient who is not taking any medi­cations, select a treatment that balances rapid stabilization with long-term efficacy and tolerability. Table 2 lists FDA-approved treatments for mania. Lamotrigine provides prophylactic efficacy with few associated risks, but it has no anti-manic effects and would be a poor choice for most actively manic patients. Most studies indicate that antipsychotics work faster than lithium at the 1-week mark; however, this may be a function of the lithium titration schedule followed in the protocols, the severity of mania among enrolled patients, the inclu­sion of typically non-responsive manic patients (eg, mixed) in the analysis, and the antipsychotic’s sedative potential rela­tive to lithium. Although the anti-manic and prophylactic potential of lithium and valproate might make them an ideal first-line option, antipsychotics could stabilize a manic patient faster, especially if agitation is present.^12,13

Breaking mania quickly is important when treating patients in the outpatient set­ting. In these situations, a reasonable choice is to prescribe a SGA, because of their rapid onset of effect, low potential for switch to depression, and utility in treating classic, mixed, or psychotic mania.¹⁰ Oral loading of valproate (20 mg/kg) is another option. An inpatient study that used an oral-loading strategy demonstrated a similar time to response as olanzapine,¹⁴ in contrast to an inpatient¹⁵ and an outpatient study¹⁶ that employed a standard starting dosage for each patient and led to slower improve­ment compared with olanzapine.

SGAs should be dosed moderately and lower than if the patient were hospitalized, to avoid alienating the patient from treat­ment by causing intolerable side effects. In particular, patients and their families should be warned about immediate risks, such as orthostasis or extrapyramidal symptoms. Although treatment guidelines recommend combination therapy as a possible first-line option,⁹ in the outpatient setting, monother­apy with an optimally dosed, rapid-acting agent is preferred to promote medication adherence and avoid potentially danger­ous sedation. Manic patients experience increased distractibility and verbal memory and executive function impairments that can interfere with medication adherence.¹⁷ Therefore, patients are more likely to fol­low a simpler regimen. If SGA or valpro­ate monotherapy does not control mania, begin combination treatment with a mood stabilizer and SGA. If the patient experi­ences remission with SGA monotherapy, the risks and benefits of maintaining the SGA vs switching to a mood stabilizer can be discussed.