Treating bipolar mania in the outpatient setting: Risk vs reward

Provide medication “as needed” for agitation—additional SGA dosing or a benzodiazepine—and explain to fam­ily members when their use is warranted. Benzodiazepines can provide short-term benefits for manic patients: anxiety relief, sedation, and anti-manic efficacy as mono­therapy^18-20 and in combination with other medications.²¹ Studies showing mono­therapy efficacy employed high dosages of benzodiazepines (lorazepam mean dos­age, 14 mg/d; clonazepam mean dosage, 13 mg/d)¹⁹ and high dosages of antipsy­chotics as needed,^18,20 and often were associ­ated with excessive sedation and ataxia.^18,19 This makes benzodiazepine monotherapy a potentially dangerous approach for out­patient treatment of mania. IM lorazepam treated manic agitation less quickly than IM olanzapine, suggesting that SGAs are preferable in the outpatient setting because rapid control of agitation is crucial.²² If pre­scribed, a trusted family member should dispense benzodiazepines to the patient to minimize misuse because of impulsivity, distractibility, desperation to sleep, or plea­sure seeking.

SGAs have the benefit of sedation but occasionally additional sleep medica­tions are required. Benzodiazepine recep­tor agonists (BzRAs), such as zolpidem, eszopiclone, and zaleplon, should be used with caution. Although these medicines are effective in treating insomnia in indi­viduals with primary insomnia²³ and major depression,²⁴ they have not been studied in manic patients. The decreased need for sleep in mania is phenomenologically²⁵ and perhaps biologically different than insomnia in major depression.²⁶ Therefore, mania-associated sleep disturbance might not respond to BZRAs. BzRAs also might induce somnambulism and other parasom­nias,²⁷ especially when used in combination with psychotropics, such as valproate²⁸; it is unclear if the manic state itself increases this risk further. Sedating antihistamines with anticholinergic blockade, such as diphenhydramine and low dosages (<100 mg/d) of quetiapine, are best used only in combination with anti-manic medi­cations because of putative link between anticholinergic blockade and manic induc­tion.²⁹ Less studied but safer options include novel anticonvulsants (gabapen­tin, pregabalin), melatonin, and melatonin receptor agonists. Sedating antidepressants, such as mirtazapine and trazodone, should be avoided.²⁵

Important adjunctive treatment steps include discontinuing all pro-manic agents, including antidepressants, stimulants, and steroids, and discouraging use of caffeine, energy drinks, illicit drugs, and alcohol. The patient should return for office visits at least weekly, and possibly more frequently, depending on severity. Telephone check-in calls between scheduled visits may be nec­essary until the mania is broken.

Psychotherapy. Other than supportive therapy and psychoeducation, other forms of psychotherapy during mania are not indicated. Psychotherapy trials in bipolar disorder do not inform anti-manic efficacy because few have enrolled acutely manic patients and most report long-term benefits rather than short-term efficacy for the index manic episode.³⁰ Educate patients about the importance of maintaining regular social rhythms and taking medication as pre­scribed. Manic patients might not be aware that they are acting differently during manic episodes, therefore efforts to improve the patient’s insight are unlikely to succeed. More time should be spent emphasizing the importance of adherence to treatment and taking anti-manic medications as pre­scribed. This discussion can be enhanced by focusing on the medication’s potential to reduce the unpleasant symptoms of mania, including irritability, insomnia, anxiety, and racing thoughts. At the first visit, dis­cuss setting boundaries with the patient to reduce mania-driven, intrusive phone calls. A patient might develop insight after mania has resolved and he (she) can appre­ciate social or economic harm that occurred while manic. This discussion might foster adherence to maintenance treatment. Advise your patient to limit activities that may increase stimulation and perpetuate the mania, such as exercise, parties, concerts, or crowded shopping malls. Also, recommend that your patient stop working temporarily, to reduce stress and prevent any manic-driven interactions that could result in job loss.

If your patient has an established relationship with a psychotherapist, discuss with the therapist the plan to initiate mania treatment in the outpatient setting and work as a collaborative team, assuming that the patient has granted permission to share information. Encourage the therapist to increase the frequency of sessions with the patient to enable greater monitoring of changes in the patient’s manic symptoms.

Family involvement
Family support is crucial when treating mania in the outpatient setting. Lacking insight and organization, manic patients require the “auxiliary” judgment of trusted family members to ensure treatment suc­cess. The family should identify a single person to act as the liaison between the family and the psychiatrist. The psychiatrist should instruct this individual to accom­pany the patient to each clinic visit and provide regular updates on the patient’s adherence to treatment, changes in symp­toms, and any new behaviors that would justify involuntary hospitalization. The treatment plan should be clearly communi­cated to this individual to ensure that it is implemented correctly. Ideally, this individ­ual would be someone who understands that bipolar disorder is a mental illness, who can tolerate the patient’s potential resentment of them for taking on this role, and who can influence the patient and the other family members to adhere to the treat­ment plan.

This family member also should watch the patient take medication to rule out nonadherence if the patient’s condition does not improve.