Savvy Psychopharmacology

When should you consider combining 2 long-acting injectable antipsychotics?

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Ms. S, age 39, with a 15-year history of schizophrenia and severe paranoid delusions, is admitted after physically assaulting a staff member at a group home. She is receiving paliperidone palmitate, 234 mg every 4 weeks. This has reduced the severity of her symptoms, but she continues to have persistent delusions that affect her ability to accept redirection from staff. Ms. S frequently accuses staff and peers of sexual assault, says that she is pregnant, and does not adhere to treatment recommendations for laboratory monitoring because the “staff uses her blood for experiments.”

Ms. S frequently requires administration of oral and IM haloperidol, as needed, when she becomes aggressive with the staff. She has poor insight into her mental illness and does not believe that she needs medication. Ms. S has a long history of stopping her oral antipsychotic after a few days, reporting that it is “harming her baby.” Monotherapy has been tried with various long-acting injectable antipsychotics (LAIAs), but she still exhibits persistent delusions. The treatment team decides to add a second LAIA, haloperidol decanoate, 200 mg every 4 weeks, to her regimen.

Treatment-resistant schizophrenia provides a challenge for practicing clinicians. Although clozapine is preferred for treatment-resistant schizophrenia,1-4 it is not an option for patients who cannot adhere to required laboratory monitoring. Treatment guidelines state that there is limited evidence for combining 2 antipsychotics (aside from augmentation of clozapine treatment) and that such use should be closely monitored and documented.2-4 Use of a single LAIA is recommended when the patient prefers the formulation or to avoid treatment nonadherence; however, treatment guidelines do not address the simultaneous use of 2 LAIAs.2,4-6 A few case reports have described successful use of dual LAIAs (Table 17-11). Five of these are summarized here (Yazdi et al10 was published in German and is only included in Table 17-11).

Ladds et al.7 A 49-year-old woman with schizophrenia who was hospitalized for aggressive and bizarre behavior and had been institutionalized for 20 years stopped taking her medication regimen.7 She started taking 8-hour showers with bleach, talking incoherently, and believing that someone was poisoning her. She had poor response to oral risperidone monotherapy; however, 2 months after adding oral fluphenazine and benztropine to her regimen, her symptoms substantially improved (doses not reported). Because she had impaired insight into the need for daily medication, she was started on depot fluphenazine decanoate and risperidone microspheres (doses not reported) before discharge. No substantial adverse effects were noted with this regimen.

Wartelsteiner and Hofer.8 A man who had been diagnosed with paranoid schizophrenia at age 20 presented with thought blocking, incoherence, persecutory delusions, and uncontrolled self-damaging behavior.8 He had been admitted 27 times over 7 years; during this time he received many antipsychotic monotherapies and combination regimens. A total of 8 oral antipsychotics (including clozapine) and 5 LAIAs had been administered during these trials. He significantly improved with the combination of olanzapine and risperidone. Both medications were switched to LAIA formulations to address medication nonadherence. His symptoms remained stable with risperidone microspheres, 100 mg, and olanzapine pamoate, 300 mg, each administered every 2 weeks. He did not experience any adverse effects with this combination therapy.

Scangos et al.9 A 26-year-old Vietnamese man with schizophrenia and an extensive history of unprovoked, psychotically driven assaults was given multiple antipsychotics (including clozapine) during hospitalizations, and his medication regimen consistently included 2 antipsychotics. After contracting viral gastroenteritis, he refused oral medications and required short-acting IM administration of both haloperidol, 5 mg, twice a day, and olanzapine, 10 mg, twice a day. Because of concerns about continuing this regimen, he was switched to haloperidol decanoate (dose not reported) and olanzapine pamoate, 405 mg, administered once per month. The injections were scheduled to alternate so that the patient would receive 1 injection every 2 weeks. The patient’s assaultive behavior was significantly reduced, and no adverse effects were reported.

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