Risperidone treatment-resistant

Depot antipsychotics (e.g., haloperidol decanoate, fluphenazine decanoate, and risperidone long-acting injection) can be used for maintenance therapy of bipolar disorder with noncompliance or treatment resistance. 

Alternatively, the current antidepressant may be augmented (potentiated) by the addition of another agent (e.g., lithium, T3), or an atypical antipsychotic (e.g., risperidone). Risperidone has been shown to be effective in combination with fluvoxamine, paroxetine, or citalopram in treatment-resistant depression. Olanzapine and fluoxetine have been found to be safe and effective in treatment-resistant depression. 

Clozapine was the first atypical antipsychotic released in the United States. However, clozapine is associated with the risk of leukopenia and, potentially, lethal agranulocytosis. Because of these concerns, hematological monitoring during clozapine pharmacotherapy is required (Alphs and Anand, 1999). Due to these hematological risks, clozapine is indicated only for patients with treatment-resistant schizophrenia. The other atypical antipsychotics, risperidone, olanzapine, quetiapine, and ziprasidone, that are marketed in the United States can be used as first-line treatments for adults with schizophrenia. 

Several reports also suggest that adjunctive risperidone (Giakas, 1995 Jacobsen, 1995 Lombroso et al., 1995 McDougle et al., 1995 Ravizza et al., 1996 Stein et al., 1997)or olanzapine (Peris and Szerman, 2000) may be helpful in treatment-resistant OCD. Systematic data in pediatric samples are needed, however, before such an approach can be recommended, and there are anecdotal reports of increased obsessions and anxiety with the atypical neuroleptics (Alzaid and Jones, 1997 Andrade, 1998 Mottard and de la Sa-blonniere, 1999). 

Studies of the use of the specific serotonin-uptake inhibitors (SSRIs) to treat OCD suggest that, compared to non-tic-related OCD, tic-related OCD is less responsive to SSRI monotherapy (McDougle et al., 1993, 1994). Addition of a neuroleptic, such as haloperidol (McDougle et ah, 1994), risperidone (McDougle et al., 2000), or olanzapine (Bogetto et al., 2000), appears to be useful in improving treatment-resistant individuals response to a SSRI. It is unclear whether this pattern of treatment response is specifically associated with a comorbid tic disorder the pattern of obsessive compulsive symptoms characteristic of TS or yet some other predictors. 

Bondolfi G, Baumann P, Paths M, et al. A randomized double-blind trial of risperidone versus clozapine for treatment-resistant chronic schizophrenia. Presented at the 148th Annual Meeting of the American Psychiatric Association, Miami, May 1995. 

Barbee JG, Comad EJ, Jamhour NJ. The effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone as augmentation agents in treatment-resistant major depressive disorder. J Clin Psychiatry 2004 65(7) 975-981. 

The concept of treatment-resistant schizophrenia, which was developed to delineate a market for the relaunch of clozapine, has lead to public acknowledgment of the extent of non-response to treatment with other neuroleptic drugs. It is now widely admitted that at least 25% of patients do not show any significant clinical improvement with drug treatment. A recent comparison of two of the newer neuroleptic drugs, risperidone and olanzapine, found that 46% and 56% of patients, respectively, did not respond after four months of treatment (Robinson et al. 2006). In addition, the majority of inpatients with psychosis are treated with other sedative drugs in addition to... 

Clozapine has also been compared with risperidone in 60 treatment-resistant patients with schizophrenia in India (16). There was clinical improvement (a more than 20% reduction from baseline PANSS scale scores) in 80% of the clozapine-treated patients and 67% of the risperidone-treated patients. The predominant adverse effects with clozapine (n = 30) were tachycardia (77%), hypersalivation (60%), sedation (60%), weight gain (43%), and constipation (30%) one patient had a seizure. The adverse effects of risperidone (n = 30) were constipation (50%), dry mouth (47%), weight gain (43%), akathisia (37%), insomnia (33%), tachycardia (30%), and impotence (27%). The final mean daily doses after 16 weeks of treatment were 343 mg for clozapine and 5.8 mg for risperidone. 

Wahlbeck K, Cheine M, Tuisku K, Ahokas A, Joffe G, Rimon R. Risperidone versus clozapine in treatment-resistant schizophrenia a randomized pilot study. Prog Neuropsychopharmacol Biol Psychiatry 2000 24(6) 911-22. 

In a 12-week, double-blind, randomized, placebo-controlled study in 40 patients with treatment-resistant schizophrenia (funded by Johnson Johnson Pharmaceutical Research Development), the addition of risperidone to clozapine improved overall symptoms and positive and negative symptoms (49). The adverse events profile of clozapine + risperidone was similar to that of clozapine + placebo. Clozapine + risperidone did not cause additional weight gain, agranulocytosis, or seizures compared with clozapine + placebo. All the patients completed 12 weeks of treatment however, the small sample size precluded definitive conclusions. 

Olanzapine, quetiapine, and risperidone are preferred alternative atypicals aripiprazole and ziprasidone are newer agents and may initially cause akathisia-like reactions clozapine is usually reserved for treatment-resistant mania or mixed states. 

Maina G, Pessina E, Albert U, Bogetto F. 8-week, single-blind, randomized trial comparing risperidone versus olanzapine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder. Eur Neuropsycho-pharmacol 2008 18(5) 364-72. 

Chouinard G, Vainer JL, Belanger M-G, et al. Risperidone and clozapine in the treatment of drug-resistant schizophrenia and neuroleptic-induced supersensitivity psychosis. Prog Neuro-Psychopharmacol Biol Psychiatry 1994 18 1129-1141. 

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