Combined typical and atypical long‐acting injectable antipsychotics in treatment‐resistant schizophrenia: Two cases

Abstract

Real-world data have shown that clozapine and long-acting injectable antipsychotics (LAIA) are more effective than oral antipsychotics in preventing relapse in schizophrenia. 1 A treatment dilemma emerges when managing patients with treatment-resistant schizophrenia (TRS) who refuse oral antipsychotics, as the treatment of choice, long-acting injectable (LAI) clozapine, is not available. We report on two patients with TRS who were successfully managed with combined typical and atypical LAIA. Informed consents have been obtained from the families of both patients.Ms A was a 35-year-old woman with TRS for 10 years (nonresponse to amisulpride 800 mg/day, risperidone 6 mg/day, and olanzapine 20 mg/day). Flupentixol decanoate 40 mg once every 2 weeks was given, because she had refused oral antipsychotics 2 years previously. Her symptoms were partially relieved, while delusion, hostility, and affective lability were still severe. LAI aripiprazole 400 mg once every 4 weeks was added, and her symptoms had improved by 3 months later. When discontinuing flupentixol decanoate, her symptoms became worse. Thus, the dose of flupentixol decanoate was maintained. Over the following 6 months, LAI aripiprazole 400 mg once every 4 weeks and flupentixol decanoate 20 mg once every 4 weeks were coadministered (an A-F-A-F sequence), and her psychotic condition was stable.Mr T was a 46-year-old man with a 20-year history of TRS due to nonresponse to several antipsychotics, including quetiapine 800 mg/day, olanzapine 20 mg/day, and haloperidol 20 mg/day. He refused any drugs, and was treated with flupentixol decanoate 40 mg once every 2 weeks over 5 years recently. He still had prominent psychotic symptoms, and therefore paliperidone palmitate 150 mg once every 4 weeks was added, significantly improving the psychotic symptoms. In the following 2 years, he was stably managed with both LAIA (a P-F-P-F sequence). Moreover, he did not experience adverse effects and was able to do some casual work.Evidence recommends that a high dose of oral antipsychotics (above the officially approved dose range) may not provide benefits for TRS, and instead increases the risk of adverse effects. 2 We have successfully managed these two TRS patients with combined typical and atypical LAIA in an alternating administration sequence; however, the improvement in Mr T might be due to paliperidone LAI alone. From a pharmacological perspective, a combination of LAIA with different receptor-binding profiles may be considered in patients with TRS who partially respond to an initial LAIA trial. 2 We hypothesized that the alternating administration scheme of two LAIA with different receptor-binding profiles may offer pharmacological benefits and reduce the risk of adverse effects. Moreover, biweekly visits provide close clinical surveillance, rigorous monitoring of psychosocial stressors, and increasing interaction with clinic staff. LAIA may uncover 'pseudoresistance' due to nonadherence to oral antipsychotics. However, the potential risk of using multiple LAIA is th...

The use of concurrent long-acting injectable antipsychotic therapy with paliperidone palmitate and aripiprazole monohydrate in a patient with schizophrenia

“…First, dual LAI therapy is only utilized in challenging cases 9 - 14 in which the use of oral antipsychotic medications has not been successful. Second, a majority of the authors 9 , 10 , 12 , 13 recommend close monitoring given the rarity of this treatment plan. Last, clinicians should consider concurrent LAI medications with varied receptor activity.…”

“…Last, clinicians should consider concurrent LAI medications with varied receptor activity. 10 , 11 , 13 …”

“…There was a total of 9 dual LAI case reports [9][10][11][12][13][14] as shown in the Table . Although there were no cases with the combination of aripiprazole and risperidone/paliperidone, there were 2 cases 13,14 of concurrent atypical LAI antipsychotics. Both cases described clinical improvement after the second atypical antipsychotic was added orally.…”

“…Several themes arose across the cases reported in the literature. First, dual LAI therapy is only utilized in challenging cases [9][10][11][12][13][14] in which the use of oral antipsychotic medications has not been successful. Second, a majority of the authors 9,10,12,13 recommend close monitoring given the rarity of this treatment plan.…”

“…Last, clinicians should consider concurrent LAI medications with varied receptor activity. 10,11,13 Augmenting risperidone/paliperidone with aripiprazole is previously described in the literature but has been largely isolated to treatment of antipsychotic-associated hyperprolactinemia. [15][16][17][18] Although our patient had no recorded episodes of galactorrhea, she did have unchanged, persistently elevated prolactin from baseline and throughout treatment with varying LAI antipsychotic regimens, including combination LAI treatment.…”