Alternatives for treating drug-induced akathisia
Akathisia remains a relatively common adverse effect of SGAs, and the profound physical distress and impaired functioning caused by akathisia necessitates pharmacologic treatment. Despite frequent use in practice for presumed benefit in akathisia, benztropine is not effective for the treatment of akathisia and the APA Guideline recommends that long-term management should begin with an antipsychotic dose reduction, followed by a switch to an agent with less propensity to incite akathisia.4 Acute manifestations of akathisia must be treated, and mirtazapine, propranolol, or clonazepam may be considered as alternatives.4 Mirtazapine is dosed 7.5 mg to 10 mg nightly for akathisia, though it should be used in caution in patients at risk for mania.4 Mirtazapine’s potent 5-HT2A blockade at low doses may contribute to its utility in treating akathisia.2 Propranolol, a nonselective lipophilic beta-adrenergic antagonist, also has demonstrated efficacy in managing akathisia, with recommended dosing of 40 mg to 80 mg twice daily.2 Benzodiazepines such as clonazepam require judicious use for akathisia because they may also precipitate or exacerbate cognitive impairment.4
Alternatives for treating TD
As mentioned above, benztropine is not recommended for the treatment of TD.1 The Box4,22,23 outlines potential treatment options for TD.
Box
Options for preventing and treating tardive dyskinesia
Monitoring is the first step in the prevention of tardive dyskinesia (TD). The American Psychiatric Association’s (APA) Practice Guideline for the Treatment of Patients with Schizophrenia recommends patients receiving first-generation antipsychotics (FGAs) be monitored every 6 months, those prescribed second-generation antipsychotics (SGAs) be monitored every 12 months, and twice as frequent monitoring for geriatric patients and those who developed involuntary movements rapidly after starting an antipsychotic.4
The APA Guideline recommends decreasing or gradually tapering antipsychotics as another strategy for preventing TD.4 However, these recommendations should be weighed against the risk of short-term antipsychotic withdrawal. Withdrawal of D2 antagonists is associated with worsening of dyskinesias or withdrawal dyskinesia and psychotic decompensation.22
Current treatment recommendations give preference to the importance of preventing development of TD by tapering to the lowest dose of antipsychotic needed to control symptoms for the shortest duration possible.22 Thereafter, if treatment intervention is needed, consideration should be given to the following pharmacological interventions in order from highest level of recommendation (Grade A) to lowest (Grade C):
A: vesicular monoamine transporter-2 inhibitors deutetrabenazine and valbenazine
B: clonazepam, ginkgo biloba
C: amantadine, tetrabenazine, and globus pallidus interna deep brain stimulation.22
There is insufficient evidence to support or refute withdrawing causative agents or switching from FGAs to SGAs to treat TD.22 Furthermore, for many patients with schizophrenia, a gradual discontinuation of their antipsychotic must be weighed against the risk of relapse.23
Valbenazine and deutetrabenazine have been demonstrated to be efficacious and are FDA-approved for managing TD. The initial dose of valbenazine is 40 mg/d. Common adverse effects include somnolence and fatigue/ sedation. Valbenazine should be avoided in patients with QT prolongation or arrhythmias. Deutetrabenazine has less impact on the cytochrome P450 2D6 enzyme and therefore does not require genotyping as would be the case for patients who are receiving >50 mg/d of tetrabenazine. The starting dose of deutetrabenazine is 6 mg/d. Adverse effects include depression, suicidality, neuroleptic malignant syndrome, parkinsonism, and QT prolongation. Deutetrabenazine is contraindicated in patients who are suicidal or have untreated depression, hepatic impairment, or concomitant use of monoamine oxidase inhibitors.22 Deutetrabenazine is an isomer of tetrabenazine; however, evidence supporting the parent compound suggests limited use due to increased risk of adverse effects compared with valbenazine and deutetrabenazine.23 Tetrabenazine may be considered as an adjunctive treatment or used as a single agent if valbenazine or deutetrabenazine are not accessible.22
Discontinuing benztropine
Benztropine is recommended as a firstline agent for the management of acute dystonia, and it may be used temporarily for drug-induced parkinsonism, but it is not recommended to prevent EPS or TD. Given the multitude of adverse effects and cognitive impairment noted with anticholinergics, tapering should be considered for patients receiving an anticholinergic agent such as benztropine. Based on their review of earlier studies, Desmarais et al5 suggest a gradual 3-month discontinuation of benztropine. Multiple studies have demonstrated an ability to taper anticholinergics in days to months.4 However, gradual discontinuation is advisable to avoid cholinergic rebound and the reemergence of EPS, and to decrease the risk of neuroleptic malignant syndrome associated with sudden discontinuation.5 One suggested taper regimen is a decrease of 0.5 mg benztropine every week. Amantadine may be considered if parkinsonism is noted during the taper. Patients on benztropine may develop rebound symptoms, such as vivid dreams/nightmares; if this occurs, the taper rate can be slowed to a decrease of 0.5 mg every 2 weeks.4
Continue to: First do no harm...