Savvy Psychopharmacology When should you consider combining 2 long-acting injectable antipsychotics? Lauren A. Diefenderfer, PharmD, BCPP s. S, age 39, with a 15-year his- treatment-resistant schizophrenia,1-4 it is not tory of schizophrenia and severe an option for patients who cannot adhere to M paranoid delusions, is admitted required laboratory monitoring. Treatment after physically assaulting a staff member guidelines state that there is limited evi- at a group home. She is receiving paliperi- dence for combining 2 antipsychotics (aside done palmitate, 234 mg every 4 weeks. This from augmentation of clozapine treatment) has reduced the severity of her symptoms, and that such use should be closely moni- Vicki L. Ellingrod, but she continues to have persistent delu- tored and documented.2-4 Use of a single PharmD, FCCP sions that affect her ability to accept redirec- LAIA is recommended when the patient Department Editor tion from staff. Ms. S frequently accuses staff prefers the formulation or to avoid treat- and peers of sexual assault, says that she is ment nonadherence; however, treatment pregnant, and does not adhere to treatment guidelines do not address the simultaneous recommendations for laboratory monitor- use of 2 LAIAs.2,4-6 A few case reports have ing because the “staff uses her blood for described successful use of dual LAIAs experiments.” (Table 1,7-11 page 43). Five of these are sum- Ms. S frequently requires administration marized here (Yazdi et al10 was published in of oral and IM haloperidol, as needed, when German and is only included in Table 1,7-11 she becomes aggressive with the staff. She page 43). has poor insight into her mental illness and does not believe that she needs medication. Ladds et al.7 A 49-year-old woman with Ms. S has a long history of stopping her oral schizophrenia who was hospitalized for antipsychotic after a few days, reporting that aggressive and bizarre behavior and had it is “harming her baby.” Monotherapy has been institutionalized for 20 years stopped been tried with various long-acting inject- taking her medication regimen.7 She started able antipsychotics (LAIAs), but she still taking 8-hour showers with bleach, talking exhibits persistent delusions. The treatment team decides to add a second LAIA, haloperi- Practice Points dol decanoate, 200 mg every 4 weeks, to her • Although treatment guidelines do regimen. not address the use of 2 long-acting Savvy Psychopharmacology injectable antipsychotics (LAIAs), is produced in partnership they recognize the need for 2 oral with the College Treatment-resistant schizophrenia pro- of Psychiatric antipsychotics in cases of treatment and Neurologic vides a challenge for practicing clinicians. resistance; however, evidence is limited. Pharmacists Although clozapine is preferred for cpnp.org • Carefully consider LAIA properties when mhc.cpnp.org (journal) Dr. Diefenderfer is Clinical Pharmacist, Center for Behavioral Medicine, choosing a regimen for dual treatment. Kansas City, Missouri. Disclosure • Use the lowest effective dose of each The author reports no financial relationships with any company LAIA to limit adverse effects and improve Current Psychiatry whose products are mentioned in this article or with manufacturers of patient tolerability of the regimen. 42 October 2017 competing products. Savvy Psychopharmacology Table 1 Published case reports of dual LAIA treatment Case report Patient Diagnosis Dual LAIA regimen Ladds et al7 Female, age 49 Schizophrenia Risperidone microspheresa Fluphenazine decanoatea Wartelsteiner Male Schizophrenia, Risperidone microspheres, 100 mg every 2 and Hofer8 paranoid type weeks Olanzapine pamoate, 300 mg every 2 weeks Scangos Vietnamese male, Schizophrenia Olanzapine pamoate, 405 mg once a month 9 et al age 26 Haloperidol decanoatea Yazdi et al10,b 44 years old Schizoaffective Risperidone microspheres, 50 mg every 2 disorder weeks Zuclopenthixol decanoate, 500 mg every 2 Clinical Point weeks A few case reports Ross and African American Schizophrenia, Paliperidone palmitate, 156 mg once a month 11 Fabian male, age 44 paranoid type Haloperidol decanoate, 400 mg every 2 have reported weeks successful use of aDose not reported bCase report published in German dual LAIAs LAIA: long-acting injectable antipsychotic incoherently, and believing that someone done. Both medications were switched to was poisoning her. She had poor response LAIA formulations to address medication to oral risperidone monotherapy; how- nonadherence. His symptoms remained ever, 2 months after adding oral fluphen- stable with risperidone microspheres, azine and benztropine to her regimen, her 100 mg, and olanzapine pamoate, 300 mg, symptoms substantially improved (doses each administered every 2 weeks. He did not reported). Because she had impaired not experience any adverse effects with this insight into the need for daily medication, combination therapy. she was started on depot fluphenazine decanoate and risperidone microspheres Scangos et al.9 A 26-year-old Vietnamese (doses not reported) before discharge. No man with schizophrenia and an exten- substantial adverse effects were noted with sive history of unprovoked, psychotically this regimen. driven assaults was given multiple anti- psychotics (including clozapine) during Wartelsteiner and Hofer.8 A man who hospitalizations, and his medication regi- had been diagnosed with paranoid schizo- men consistently included 2 antipsychotics. phrenia at age 20 presented with thought After contracting viral gastroenteritis, he blocking, incoherence, persecutory delu- refused oral medications and required sions, and uncontrolled self-damaging short-acting IM administration of both hal- behavior.8 He had been admitted 27 times operidol, 5 mg, twice a day, and olanzap- over 7 years; during this time he received ine, 10 mg, twice a day. Because of concerns many antipsychotic monotherapies and about continuing this regimen, he was combination regimens. A total of 8 oral switched to haloperidol decanoate (dose antipsychotics (including clozapine) and not reported) and olanzapine pamoate, 5 LAIAs had been administered during 405 mg, administered once per month. The these trials. He significantly improved with injections were scheduled to alternate so Current Psychiatry the combination of olanzapine and risperi- that the patient would receive 1 injection Vol. 16, No. 10 43 Savvy Psychopharmacology Table 2 Summary of long-acting antipsychotic properties a Drug Dose range (mg) Frequency Injection site(s) T1/2 (days) Adverse effects Monitoring First-generation antipsychotics Fluphenazine 12.5 to 100 Every 2 to 4 weeks Gluteal or deltoid Approximately 14 Extrapyramidal symptoms, Hypotension, tardive decanoate12 hypertension, drowsiness dyskinesia Haloperidol 10 to 15 times Every 4 weeks Gluteal or deltoid Approximately 21 Tachycardia, hypotension, Hypotension, tardive decanoate13 oral dose hypertension, extrapyramidal dyskinesia symptoms Second-generation antipsychotics Aripiprazole 160 to 400 Monthly Gluteal or deltoid Approximately 46.5 Weight gain, akathisia, Metabolic monitoring, monohydrate14 injection site pain, sedation tardive dyskinesia Clinical Point Aripiprazole 441 to 882 Monthly, or every 6 Gluteal, deltoid 29.2 to 34.9 Akathisia Metabolic monitoring, lauroxil15 weeks (882 mg only) (441 mg only) tardive dyskinesia Prior to initiating Olanzapine 150 to 405 Every 2 or 4 weeks Gluteal 30 Headache, sedation, weight 3-hour post-injection treatment with pamoate16 gain, cough, diarrhea, back observation at pain, nausea, somnolence, registered health care 2 LAIAs, previous dry mouth, nasopharyngitis, facility, metabolic tolerability of each increased appetite, vomiting monitoring, tardive dyskinesia medication must be Paliperidone 39 to 234 Every 4 weeks Gluteal or deltoid 25 to 49 Injection site reactions, Metabolic monitoring, confirmed palmitate (1 month)17 somnolence/sedation, tardive dyskinesia dizziness, akathisia, extrapyramidal disorder Paliperidone 273 to 819 Every 3 months Gluteal or deltoid 84 to 95 (deltoid) or Injection site reaction, weight Metabolic monitoring, palmitate (3 month)18 118 to 139 (gluteal) gain, headache, upper tardive dyskinesia respiratory tract infection, akathisia, parkinsonism Risperidone 12.5 to 50 Every 2 weeks Gluteal or deltoid 3 to 6 Headache, parkinsonism, Metabolic monitoring, microspheres19 dizziness, akathisia, fatigue, tardive dyskinesia constipation, dyspepsia, sedation, weight gain, pain in extremity, dry mouth aFor second-generation agents in clinical trials of patients with schizophrenia at rates >5% every 2 weeks. The patient’s assaultive What to consider before initiating behavior was significantly reduced, and no dual LAIA treatment adverse effects were reported. Evaluate the frequency of administration, flexibility of dosing, administration site, Ross and Fabian.11 An African American adverse effects, and monitoring require- man, age 44, was receiving haloperidol ments of each LAIA (Table 212-19) to ensure decanoate, 400 mg every 2 weeks, and oral the patient’s optimal tolerability of the regi- haloperidol, 20 mg/d.11 Because of residual men. Previous tolerability of each medica- Discuss this article at symptoms, a history of nonadherence, and tion must be confirmed by evaluating the www.facebook.com/ concerns about increasing the haloperidol patient’s medication history or oral or IM CurrentPsychiatry decanoate dose or frequency, oral haloperi- administration of each agent prior to initiat- dol was discontinued and paliperidone pal-