Antipsychotics in adults with schizophrenia: comparative effectiveness of first-generation versus second-generation medications: a systematic review and meta-analysis.

BACKGROUND: Debate continues about the comparative benefits and harms of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) in treating schizophrenia. PURPOSE: To compare the effects of FGAs with those of SGAs in the treatment of adults aged 18 to 64 years with schizophrenia and related psychosis on illness symptoms, diabetes mellitus, mortality,tardive dyskinesia, and a major metabolic syndrome. DATA SOURCES: English-language studies from 10 electronic databases to March 2012, reference lists of relevant articles, and gray literature. STUDY SELECTION: Randomized trials for efficacy and cohort studies at least 2 years in duration for adverse events. DATA EXTRACTION: Two independent reviewers extracted data from 114 studies involving 22 comparisons and graded the strength of evidence for primary outcomes as insufficient, low, moderate, or high using the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SYNTHESIS: Few differences of clinical importance were found for core illness symptoms; lack of precision in effect estimates precluded firm conclusions for many comparisons. Moderate-strength evidence showed a clinically important benefit of haloperidol over olanzapine for improving positive symptoms, but the benefit was scale-dependent: It was seen when the Scale for the Assessment of Positive Symptoms was used but not when the Positive and Negative Syndrome Scale (PANSS) was used. Moderate-strength evidence showed a clinically important benefit of olanzapine over haloperidol in improving negative symptoms when the PANSS and the Scale for the Assessment of Negative Symptoms were used. Low-strength evidence showed no difference in mortality for chlorpromazine verus clozapine or haloperidol versus aripiprazole,increased incidence of the metabolic syndrome for olanzapine versus haloperidol (risk differences, 2% and 22%), and higher incidence of tardive dyskinesia for chlorpromazine versus clozapine (risk differences, 5% and 9%). Evidence was insufficient to draw conclusions for diabetes mellitus. LIMITATIONS: All studies had high or unclear risk of bias. Length of study follow-up was often too brief to adequately measure adverse events. Medication comparisons, dosage, and outcome measurement were heterogenous for head-to-head comparisons. Selective patient populations limit generalizability. CONCLUSION: Clear benefits of FGAs versus SGAs for treating schizophrenia remain inconclusive because of variation in assessing outcomes and lack of clinically important differences for most comparisons. The strength of evidence on safety for major medical events is low or insufficient. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Antipsychotics for children and young adults: a comparative effectiveness review.

BACKGROUND AND OBJECTIVE: Despite increasing on-label and off-label use of antipsychotics, prescribing antipsychotics to children remains controversial due to uncertainty of their relative benefits and safety. We systematically reviewed the effectiveness and safety of first- (FGA) and second-generation antipsychotics (SGA) for patients aged ≤24 years with psychiatric and behavioral conditions. METHODS: We searched 10 databases from January 1987 to February 2011, gray literature, trial registries, and reference lists. Two reviewers independently selected studies, assessed methodologic quality, and graded the evidence. One reviewer extracted, and a second verified, data. We summarized findings qualitatively and conducted meta-analyses when appropriate. RESULTS: Sixty-four trials and 17 cohort studies were included. Most trials had a high risk of bias; cohort studies had moderate quality. All comparisons of FGAs versus SGAs, FGAs versus FGAs, and FGAs versus placebo had low or insufficient strength of evidence. There was moderate strength of evidence for the following comparisons. Olanzapine caused more dyslipidemia and weight gain, but fewer prolactin-related events, than risperidone. Olanzapine caused more weight gain than quetiapine. Compared with placebo, SGAs improved clinical global impressions (schizophrenia, bipolar and disruptive behavior disorders) and diminished positive and negative symptoms (schizophrenia), behavior symptoms (disruptive behavior disorders), and tics (Tourette syndrome). CONCLUSIONS: This is the first comprehensive review comparing the effectiveness and safety across the range of antipsychotics for children and young adults. The evidence on the comparative benefits and harms of antipsychotics is limited. Some SGAs have a better side effect profile than other SGAs. Additional studies using head-to-head comparisons are needed.

Comparative effectiveness of pain management interventions for hip fracture: a systematic review.

BACKGROUND: Pain management is integral to the management of hip fracture. PURPOSE: To review the benefits and harms of pharmacologic and nonpharmacologic interventions for managing pain after hip fracture. DATA SOURCES: 25 electronic databases (January 1990 to December 2010), gray literature, trial registries, and reference lists, with no language restrictions. STUDY SELECTION: Multiple reviewers independently and in duplicate screened 9357 citations to identify randomized, controlled trials (RCTs); nonrandomized, controlled trials (non-RCTs); and cohort studies of pain management techniques in older adults after acute hip fracture. DATA EXTRACTION: Independent, duplicate data extraction and quality assessment were conducted, with discrepancies resolved by consensus or a third reviewer. Data extracted included study characteristics, inclusion and exclusion criteria, participant characteristics, interventions, and outcomes. DATA SYNTHESIS: 83 unique studies (64 RCTs, 5 non-RCTs, and 14 cohort studies) were included that addressed nerve blockade (n = 32), spinal anesthesia (n = 30), systemic analgesia (n = 3), traction (n = 11), multimodal pain management (n = 2), neurostimulation (n = 2), rehabilitation (n = 1), and complementary and alternative medicine (n = 2). Overall, moderate evidence suggests that nerve blockades are effective for relieving acute pain and reducing delirium. Low-level evidence suggests that preoperative traction does not reduce acute pain. Evidence was insufficient on the benefits and harms of most interventions, including spinal anesthesia, systemic analgesia, multimodal pain management, acupressure, relaxation therapy, transcutaneous electrical neurostimulation, and physical therapy regimens, in managing acute pain. LIMITATIONS: No studies evaluated outcomes of chronic pain or exclusively examined participants from nursing homes or with cognitive impairment. Systemic analgesics (narcotics, nonsteroidal anti-inflammatory drugs) were understudied during the search period. CONCLUSION: Nerve blockade seems to be effective in reducing acute pain after hip fracture. Sparse data preclude firm conclusions about the relative benefits or harms of many other pain management interventions for patients with hip fracture. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Systematic review: nonoperative and operative treatments for rotator cuff tears.

BACKGROUND: Many approaches exist for managing rotator cuff tears. PURPOSE: To compare the benefits and harms of nonoperative and operative interventions on clinically important outcomes in adults with rotator cuff tears. DATA SOURCES: 12 electronic databases (1990 to September 2009), gray literature, trial registries, and reference lists were searched. STUDY SELECTION: Controlled and uncontrolled studies that assessed nonoperative or operative treatments or postoperative rehabilitation for adults with confirmed rotator cuff tears were included. Operative studies in English-language publications and nonoperative and postoperative rehabilitation studies in English, French, or German were considered. Studies were assessed in duplicate. DATA EXTRACTION: 2 reviewers assessed risk for bias by using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale. One reviewer rated the evidence by using a modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Data were extracted by one reviewer and verified by another. DATA SYNTHESIS: 137 studies met eligibility criteria. All trials had high risk for bias. Cohort and uncontrolled studies were of moderate quality. Reported functional outcomes did not differ between open versus mini-open repair, mini-open versus arthroscopic repair, arthroscopic repair with versus without acromioplasty, or single-row versus double-row fixation. Earlier return to work was reported for mini-open repair versus open repair and for continuous passive motion with physical therapy versus physical therapy alone. Open repairs showed greater improvement in function than did arthroscopic debridement. Complication rates were low across all interventions. LIMITATIONS: Limited evidence, which was often of low quality, precluded conclusions for most comparisons. Language restrictions may have excluded some relevant studies, and selective outcome reporting may have introduced bias. CONCLUSION: Evidence on the comparative effectiveness and harms of various operative and nonoperative treatments for rotator cuff tears is limited and inconclusive. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.