36 Psychosomatic Medicine C LINICAL P SYCHIATRY N EWS • September 2008 Agent May Ease Parkinson’s Symptoms

BY PATRICE WENDLING ease and psychosis and received either pi- There was no clinically significant dif- Chicago Bureau mavanserin (n = 29) or placebo (n = 31) ference between patients treated with Improvement of Psychosis on an outpatient basis for 28 days, starting placebo vs. pimavanserin in absolute mean In Patients With C HICAGO — The investigational agent at 20 mg daily on day 1, with dose escala- change from baseline to day 28 in UPDRS Parkinson’s Disease pimavanserin appears to lessen the symp- tions to 40 mg and 60 mg on day 8 and 15, motor scores (–3.05 vs. –1.24) or activities toms of psychosis in patients with Parkin- respectively, depending on individual clin- of daily living scores (–2.51 vs. –0.70). son’s disease without worsening motor ical response. No differences were observed between 40% function, according to data from a multi- Patients treated with pimavanserin groups on the Schwab and England Activ- Improvement center randomized demonstrated a 40% ities of Daily Living Scale part of the UP- on Scale for the Assessment phase II trial involv- Adverse events commonly improvement in the DRS or the Clinical Global Impression of Positive ing 60 patients. Scale for the Assess- Scale severity of illness subscale. Symptoms Pimavanserin is a experienced with ment of Positive The most common adverse events in pa- potent, active 5-hy- and —such as Symptoms (SAPS) tients treated with pimavanserin were EWS droxytryptamine 2a combination score somnolence, edema, and increased blood N somnolence, fatigue, and 11% (5-HT2a) for hallucination and urea—each occurring in three patients, the , dizziness—were uncommon delusion, as com- authors wrote. EDICAL according to Dr. Rev- pared with an 11% In a second poster presented at the M with pimavanserin. Pimavanserin Placebo ell of Acadia Phar- improvement for pa- meeting, pimavanserin was well tolerated (n = 29) (n = 31) LOBAL G maceuticals Inc., tients treated with and did not worsen Parkinsonism symp- Note: Based on a 28-day treatment. which sponsored the study. However, it placebo, Dr. Stephen Revell and associates toms in 39 patients (mean age 72 years) Source: Dr. Revell LSEVIER lacks the receptor (D2) and his- reported in a poster at the 12th Interna- with Parkinson’s and psychosis at doses up E tamine receptor (H1) binding that are tional Congress of Parkinson’s Disease to 60 mg/day for up to 42 months (mean linked to intolerable adverse effects of and Movement Disorders. 14 months). Adverse events commonly sored, open-label extension safety study. other . Pimavanserin is be- Statistically significant improvements experienced with clozapine and quetiap- Only one patient who experienced som- ing developed as a cotherapy for schizo- also were observed for patients treated ine—such as somnolence, fatigue, and nolence discontinued pimavanserin treat- phrenia, as well as for Parkinson’s disease with pimavanserin on the mentation, be- dizziness—were uncommon with pima- ment. A single case of rhabdomyolysis psychosis. havior, and mood part of the Unified vanserin, according to Dr. Roger Mills, was the only serious adverse event consid- Patients in the study had Parkinson’s dis- Parkinson’s Disease Rating Scale (UPDRS). also of Acadia, who led the industry-spon- ered to be possibly treatment-related. ■ and SSRIs Show for Insomnia Is Common Treatment of Irritable Bowel Syndrome During Chemotherapy

BY KERRI WACHTER BY LISA ZAMOSKY sipramine in a placebo-controlled cacy of SSRIs in the treatment of Senior Writer Contributing Writer 12-week study (Gastroenterology IBS. One study compared paroxe- 2003;125:19-31). Patients had mod- tine with psychotherapy and usu- C HICAGO — The prevalence of insomnia is roughly three S AN D IEGO — There is a strong erate to severe functional bowel al medical treatment by a gas- times greater among cancer patients than it is among the gen- rationale as well as some evidence disorders and most met the crite- troenterologist (Gastroenterology eral population, according to a secondary analysis of more supporting the use of an- ria for IBS. The researchers started 2003;124:303-17). The investigators than 500 patients. tidepressants and selective sero- patients at 50 mg of , found that both paroxetine and The prevalence of insomnia that meets clinical criteria was tonin reuptake inhibitors for the moving them up to 100 mg and psychotherapy reduced pain scores 45.6% among cancer patients receiving chemotherapy, which treatment of irritable bowel syn- then 150 mg during the course of and improved health-related qual- compares with 19% in the general population. An additional drome, Dr. Lin Chang said at the the study. ity of life compared with usual 35% of cancer patients had insomnia symptoms, compared annual Digestive Disease Week. In the IBS patients, 62.5% of medical treatment. This study was with 15% in the general population, reported Oxana Palesh, Dr. Chang, a gastroenterologist those on desipramine had im- the first to show that SSRIs are an Ph.D., a radiation oncologist at the University of Rochester with the Center for Neurovisceral provement of their symptoms, effective treatment for functional (N.Y.), at the annual meeting of the American Society of Clin- Sciences and Women’s Health at compared with 37.5% of those on gastrointestinal disorders. ical Oncology. the University of California, Los placebo. Only patients who com- In the other study, investigators Roughly 80% of the patients continued to have insomnia Angeles’ division of digestive dis- pleted treatment were included. conducted a crossover trial on IBS problems throughout chemotherapy. “So insomnia does not eases, discussed the theoretical ba- Most patients with IBS have patients, comparing 6 weeks of go away on its own,” she said. sis and the available research data chronic functional abdominal pain treatment with citalopram (3 weeks The researchers also found that the prevalence of insomnia supporting the use of selective that is very difficult to treat, ac- at 20 mg, 3 weeks at 40 mg) with was greatest among lung cancer patients (P less than .05). In serotonin reuptake inhibitors and cording to Dr. Chang. “Tricyclics placebo (Gut 2006;55:1095-103). addition, younger patients tended to have more insomnia (P tricyclic (TCAs) for can be beneficial in IBS,” she con- Following 3 and 6 weeks of treat- less than .05). The researchers found no difference in the preva- treating irritable bowel syndrome. cluded, stating that because of ment, there was significant im- lence of insomnia between male and female cancer patients. First, the majority of IBS pa- their anticholinergic effects, TCAs provement in the group given For the original study, 832 cancer patients were assessed dur- tients seen in a referral practice— have been shown to improve IBS citalopram with respect to abdom- ing chemotherapy cycles 1 and 2. as many as 60%—have some type symptoms. inal pain, bloating, the impact of Those found to have fatigue (547 patients) were random- of psychological disturbance, such Dr. Chang pointed out that the symptoms on daily life, and overall ized to receive either 20 mg paroxetine or placebo. Insomnia as depression, anxiety, personality desipramine study, while demon- well-being. The impact on stool was assessed using the Hamilton Rating Scale for Depression difficulties, or life stress. strating a benefit, utilized a very pattern, however, was only moder- (cycles 1, 2, 3, 4), and depression was assessed using the Cen- Second, one of the key mecha- high dose of TCAs at the outset ate. “There is evidence, separate ter for Epidemiologic Studies–Depression scale. Fatigue was nisms of IBS involves alterations in with patients, something that she from mood, that SSRIs may help GI assessed using the Fatigue Symptom Checklist and the Mul- the brain-gut interaction. As a re- finds difficult to implement in symptoms,” Dr. Chang concluded. tidimensional Assessment of Fatigue. sult, TCAs and SSRIs may be able practice. “IBS patients have a lot Although literature supporting Patients were mostly female (72%) and white (89%), with to change visceral sensitivity and of drug sensitivity, so I start at a the use of TCAs and SSRIs is lack- a mean age of 57 years. Half had breast cancer, and overall motor activity, or both. Finally, lower dose. I tell them that they ing, she said that other medica- 64% were undergoing adjuvant therapy. Fatigue and depres- both of these classes of medication may not see an effect [right away] tions used for IBS have not been ef- sion data were previously reported (J. Clin. Oncology appear to help regulate pain. but that they may want to start fective and that these medications 2003;21:4635-41). Although paroxetine did improve depressive During her talk, Dr. Chang dis- slower and titrate it up. The slow- seem to work. She said she takes symptoms, it had no effect on fatigue. In this analysis, the re- cussed one of the largest studies er you go, the fewer side effects care of patients with “very severe” searchers reported that paroxetine had no significant effect on on TCAs for the treatment of IBS, you’ll have.” conditions, “which means you insomnia, compared with placebo. in which the investigators evaluat- Dr. Chang also discussed two have to think outside of the box; Dr. Palesh reported that she has no relevant financial rela- ed the efficacy of the TCA de- studies that demonstrated the effi- you have to be creative.” ■ tionships. ■

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