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REVIEW Table 1: Efficacy of typical antipsychotics in treatment of DOP 10 Study Hamann and Avnstorp 1982 15 Ungvari and Vlader 1986 13 Sample Size Treatment Dose Duration of treatment or follow-up Number of patients with full or partial remission (%) Number of patients with no change in symptoms (%) n=11 Pimozide 1-5 mg/day 6 weeks 10 (91 1 (9) 0 Number of patients with deterioration of condition (%) Additional notes n=9 Placebo N/A 4 weeks 1 (9) 0 8 (73) Two lost to follow-up for senility (n=1) and extensive relapse (n=1) n=10 Pimozide 2-8 mg/day 3 weeks 10 (100) 0 0 n=10 Placebo N/A 2 weeks 0 1 (10) 9 (90) Zomer et al. 1998 16 n=18 Pimozide 1-5 mg/day 3-4 weeks 11 (61) 0 7 (39) n=15 None N/A 3 (20) 12 (80) 0 Lyell 1983 17 n=66 Pimozide 2-12 mg/day N/A 44 (67) 16 (24) 0 6 lost to follow-up Bhatia et al. 2000 18 n=46 Pimozide 4-8 mg/day N/A 40 (87) 0 6 (13) Lindskov and Baadsgaard 1985 19 n=14 Pimozide Unknown 19-48 weeks after termination of treatment Table 2: Efficacy of atypical antipsychotics in treatment of DOP Atypical Antipsychotic Treatment Sample Size Dose Number of patients with full or partial remission (%) Number of patients with no change in symptoms (%) 7 (50) 0 4 (29) Three patients with relapses but responded to intermittent treatment Number of patients with deterioration of condition (%) Number of patients lost to follow up (%) Risperidone 24-28 41 0.25-5 mg/day 28 (68) 1 (2) 0 7 (29) lost to follow up; 4 were switched to other drugs for varying reasons including requiring a different antipsychotic for co-morbid psychiatric disease, and intolerance of risperidone; 1 took it once and refused to continue medication Olanzapine 25,26,28 10 2.5-20 mg/day 9 (90) 0 0 1 (10) Quetiapine 27, 28 2 100-150 mg/day 2 (100) 0 0 Aripiprazole 30-32 4 10-15 mg/day 3(75) 0 0 1 (25) Paliperidone 33 1 3 mg/day 1 (100) 0 0 RLAI 29 1 25-37.5 mg IM 1 (100) 0 0 while 3 patients were non-compliant with treatment. 10 Of note, the sample sizes for the other typical antipsychotic treatments were relatively small. atypical antipsychotics Atypical antipsychotics differ from typical antipsychotics in their various mechanisms of action and are generally associated with less extrapyramidal symptoms. Meltzer et al. (1989) 20 proposed that a preference for 5-HT2A receptor antagonism rather than DA D2 receptor antagonism distinguishes this class of drugs, although a number of other hypotheses question this. 21, 22 Atypical antipsychotics used in the treatment of DP that will be discussed are risperidone, olanzapine, quetiapine, aripiprazole, and paliperidone (Table 2). A number of case series have utilized risperidone as the main treatment modality for DP. Gallucci and Beard23 first established risperidone as a potential treatment of DP. Overall, of the 41 cases of DP treated with risperidone that we reviewed, 28 had a full or partial remission, one had no change in symptoms and 12 were lost to follow up or were switched to another drug during the treatment course – reasons for switching medications include co-morbidities that could be simultaneously treated with DP using another drug and unspecified intolerance of risperidone (Table 2). 24-28 The most recent and largest retrospective case study followed 20 patients utilizing atypical antipsychotics for DP. 26 Fifteen patients were treated with risperidone as the main atypical antipsychotic and 10 of them had full or partial remission, while 5 were lost to follow-up. Five patients were treated with olanzapine as the main atypical University of <strong>Alberta</strong> Health Sciences Journal • April 2012 • Volume 7 • Issue 1
antipsychotic. Of these patients, 4 had full or partial remission, and 1 was lost to follow up. Another case series compared 4 patients treated with risperidone and one treated with quetiapine. 27 Three of the 4 risperidone-treated patients experienced total resolution of delusions; one of these three patients was also on lithium, another was on sertraline and alprazolam as well, and another was also on sertraline and donepezil. The last risperidone treated patient had a decrease in delusions and was on no other medications. The patient treated with quetiapine showed partial remission and was also on venlafaxine, clonazepam, buspirone and bupropion. Shah and Pervez (2009) published only the second case report for the use of risperidone long-acting injections (RLAI). 29 The patient refused to take oral risperidone, but accepted RLAI 25 mg IM every 2 weeks. This dosage was titrated up to 37.5 mg IM on discharge and she then switched to 5 mg/day PO risperidone. Her symptoms improved, although complete remission was not achieved. There are also newer atypical antipsychotics whose efficacy in the treatment of DP has only been documented in a limited number of case studies. One example is aripiprazole. 30-32 Rocha and Hara (2007) documented the first case of aripiprazole treatment in an 85 year old DP patient and she underwent full remission. 30 In a subsequent study, 2 patients with DP were treated with aripiprazole and both had complete remission. 31 Paliperidone, an atypical antipsychotic approved by the FDA in 2006, has only been used in one DP case, where an 88 year old man treated with the drug underwent complete remission. 33 DISCUSSION Our review of typical antipsychotics indicates that pimozide is an effective treatment option for DP. The rates of full or partial remission were similar to the numbers reported in a systematic review by Lepping et al. (2007). 10 There have been a number of smaller case reports and studies utilizing other typical antipsychotics such as haloperidol, trifluoperazine, flupenthixol and fluphenazine depot, all of which showed excellent rates of full or partial remission. 10 Despite the past successes of pimozide, it is no longer considered first-line treatment of DP, due to the advent of the safer atypical antipsychotics. 34 Furthermore, the long-term use of pimozide is associated with a number of adverse side effects. Extrapyramidal symptoms such as tardive dyskinesia, parkinsonism and akathisia occur in less than 10-15% of patients treated with pimozide for schizophrenia, and Gilles de la Tourette Syndrome. 11 It has also been associated with clinically significant QT interval c prolongation, including Torsades de Pointes, possibly due to the calcium channel blocking effects of the drug. 7, 14, 35 These side effects, especially its cardiac effects and drug interactions (drugs metabolized by cytochrome P450 isoenzyme 3A4), make pimozide a non-ideal DP therapy. 34 Much less is known about atypical antipsychotics, because of their relatively recent introduction compared to typical antipsychotics. The largest review to date of atypical antipsychotic use in DP was conducted in 2008 by Freudenmann and Lepping, 34 which concluded that atypical antipsychotics should be the first line therapy for DP. The atypical antipsychotics with the largest sample sizes in our review were risperidone and olanzapine. Risperidone has been established as the most common atypical antipsychotic used in the treatment of DP. The particular effectiveness of this drug has been linked to its high affinity for 5-HT2 receptors, a receptor which has been linked to psychotic processes and perceptual differences. 12 Although risperidone’s side effect profile is superior to that of typical antipsychotics, there are instances where parkinsonism and akathisia have been produced by its use and it has been associated with a mild increase in metabolic syndrome. 32 An added benefit of risperidone is that it is the only atypical antipsychotic available as a long-acting depot. Long acting injections are particularly useful in patients who are demonstrating harmful behaviours and refusing to comply with oral treatment. The goal of such a treatment would be to help the patient accept their problem is psychological and thus comply with oral therapy. Olanzapine is the second most common atypical antipsychotic used in DP treatment. 34 Its side effect profile is also superior to that of pimozide and it rarely causes extrapyramidal syndrome. However, this medication is closely associated with metabolic syndrome and sedation. 32 Its use is still limited by a smaller body of evidence, but the fact that three patients treated with risperidone were switched to olanzapine due to intolerance suggests it may be a more tolerable drug. 25 Quetiapine had an excellent remission rate, but with a small sample size (n=2), more studies must be done in order to assess its use in the treatment of DP. Freudenmann and Lepping (2008) found a full or partial remission rate of 88% after reviewing 8 cases. 34 The side effect profile of quetiapine is generally limited to drowsiness, dizziness and postural hypotension, with minimal risk of extrapyramidal symptoms or adverse cardiac effects. 36 Quetiapine’s excellent side effect profile combined with its high remission rate makes it a potential treatment for DP. The results of aripiprazole treatment in DP have only been published for 4 patients to date with all 4 demonstrating full or partial remission. 23-25 There have not been any randomized control trials or placebo cross over studies performed with aripiprazole and DP, but the case study results are promising. Adverse effects of aripiprazole include nausea and akathisia, but it is nonsedating and less often associated with extrapyramidal symptoms and metabolic disturbances. 37 This excellent side effect profile may make it beneficial to DP patients who cannot tolerate the side effects of other antipsychotics. Paliperidone is the latest atypical antipsychotic used in the treatment of DP. Paliperidone is the main active metabolite of risperidone and it blocks 5-HT and D - 2A 2 receptors. It has a long half-life of 24 hours, which decreases the number of daily doses. As well, it decreases the risk of any potential adverse drug reactions, which is especially important because many DP patients have numerous co-morbidities being treated simultaneously. 33 The clinical efficacy of paliperidone as a treatment for DP needs to be confirmed by further case studies or randomized control trials. CLINICAL IMPLICATIONS Diagnosis of DP is definitely within the scope of a dermatology practice. However, the psychological basis of the disorder makes initiating therapy in a dermatologist office challenging. Patients often feel as if their symptoms are not being seriously considered when the dermatologist tries to explain that the disease is psychotic in nature. Referral to a psychiatrist is often met with anger and frustration, resulting in the patient either seeking the opinion of another dermatologist or resorting to self-treatment, which may be potentially harmful. 10 It may be prudent to ask the patient’s thoughts on you consulting an expert colleague who deals with similar conditions more frequently. This will open the door to discussing the management plan with a psychiatrist, while empowering the patient to be actively involved in the treatment decision. University of <strong>Alberta</strong> Health Sciences Journal • April 2012 • Volume 7 • Issue 1 11 REVIEW
Page 1 and 2: UAHSJ www.uahsj.ualberta.ca ISSN 17
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Page 39 and 40: Thank you The UAHSJ wishes to thank

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