Antidepressants in the treatment for chronic low back pain: questioning the validity of meta-analyses.

OBJECTIVES: To contrast the analgesic effect of duloxetine with antidepressants reported in other published randomized clinical trials (RCTs) and review articles in patients with chronic low back pain (CLBP). METHODS: In this narrative review, the results of 13 RCTs and 5 systematic reviews examining the analgesic effect of various antidepressants in CLBP were contrasted with those of 3 placebo-controlled duloxetine RCTs. Treatment effects based on the Brief Pain Inventory (BPI) average score in the duloxetine RCTs were assessed in all completers (by study and overall) and in last-observation-carried-forward (LOCF) analyses (extracted from study reports). 30%- and 50%-reduction response rates were compared between duloxetine and placebo. RESULTS: Eleven different antidepressants were examined in 13 individual RCTs. Sample sizes, treatment durations, and analysis methods varied across studies. Reviews each included 5 to 9 of the RCTs and came to different conclusions regarding the analgesic effect of antidepressants: 2 found no evidence while 3 reported some evidence. The completer analysis showed greater improvements in BPI average scores with duloxetine vs. placebo (significant in 2 studies). Overall, the least square mean (standard error) difference between treatments was - 0.7 (0.15) (P < 0.0001). Overall response rates were significantly larger with duloxetine than with placebo. CONCLUSIONS: Due to the diversity of previous studies and the pooling methods used, the conclusions regarding the analgesic effect of antidepressants in CLBP drawn from systematic reviews must be interpreted with caution. Appropriately designed and powered studies similar to recently published duloxetine studies are recommended to demonstrate the analgesic effect of antidepressants.

Brain activity during emotionally negative pictures in schizophrenia with and without flat affect: an fMRI study.

The aim of this functional magnetic resonance imaging (fMRI) study was to compare regional brain activity in schizophrenia subjects with (FA+) and without (FA-) flat affect during the viewing of emotionally negative pictures. Thirteen FA+ subjects and 11 FA- subjects were scanned while being presented with a series of emotionally negative and neutral pictures. Experientially, the viewing of the negative pictures induced a negative emotional state whose intensity was significantly greater in the FA- group than in the FA+ group. Neurally, the Negative minus Neutral contrast revealed, in the FA- group, significant loci of activation in the midbrain, pons, anterior cingulate cortex, insula, ventrolateral orbitofrontal cortex, anterior temporal pole, amygdala, medial prefrontal cortex, and extrastriate visual cortex. In the FA+ group, this contrast produced significant loci of activation in the midbrain, pons, anterior temporal pole, and extrastriate visual cortex. When the brain activity measured in the FA+ group was subtracted from that measured in the FA- group, only the lingual gyrus was significantly activated. Perhaps in FA+ subjects an amygdaloid malfunction rendered the amygdala unable to correctly evaluate the emotional meaning of the pictures presented, thus preventing effective connectivity linking the amygdala to the brain regions implicated in the physiological and experiential dimensions of emotion. Alternatively, a disturbance of effective connectivity in the neural networks linking the midbrain and the medial prefrontal system may have been responsible for the quasi absence of emotional reaction in FA+ subjects, and the abnormal functioning of the medial prefrontal cortex and anterior cingulate cortex in the FA+ group.

Clinical experience with duloxetine in the management of chronic musculoskeletal pain. A focus on osteoarthritis of the knee.

Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with central nervous system activity. Its analgesic efficacy in central pain is putatively related to its influence on descending inhibitory pain pathways. The analgesic efficacy of duloxetine has been demonstrated in four distinct chronic pain conditions. These include neuropathic pain associated with diabetic peripheral neuropathy, fibromyalgia, chronic low back pain, and osteoarthritis knee pain (OAKP). The purpose of this review is to examine the clinical efficacy and safety of duloxetine in the management of chronic OAKP. Three separate randomized, double-blind placebo-controlled trials have demonstrated that (1) a clinically meaningful decrease in pain severity occurs at about 4 weeks relative to placebo, (2) patients receiving duloxetine report better improvements in physical functioning relative to placebo, (3) duloxetine is safe and effective when used adjunctively with nonsteroidal anti-inflammatory drugs, and (4) that there are no new safety signals beyond what has been observed in other indications.

Dissociating medication effects from learning and practice effects in a neurocognitive study of schizophrenia: Olanzapine versus haloperidol.

OBJECTIVE: To contrast the effect of a typical antipsychotic (haloperidol) and an atypical antipsychotic (olanzapine) on neurocognitive functioning in schizophrenia when learning and practice (LP) effects are controlled. METHODS: Two groups of participants were recruited, 27 schizophrenia patients in their first 5 years of illness and 13 normal controls. Prior to double-blind randomisation, all subjects were assessed on four occasions within 5 days (prerandomisation period) on the same neurocognitive battery. Repeated assessment prior to randomisation was chosen as a method to control for LP effects. Patients were then randomised to 56 days of treatment with haloperidol or olanzapine (postrandomisation). All subjects were assessed on neurocognitive measures at Days 28 and 56. RESULTS: LP effects were present during the prerandomisation period on motor tasks, verbal and visual short-term memory, attention, and on a measure of verbal working memory. There were no changes in performance for patients randomised to treatment with olanzapine or haloperidol or the normal control group during the postrandomisation period. CONCLUSIONS: Once LP effects are controlled, olanzapine and haloperidol do not affect performance on measures of motor functioning, verbal short-term memory, attention, verbal working memory, reaction time, visuospatial short-term memory, and visual working memory beyond that observed from LP effects.

Intrusion errors in explicit memory: their differential relationship with clinical and social outcome in chronic schizophrenia.

INTRODUCTION: Memory deficits might account for clinical and adaptive differences between groups of patients with chronic schizophrenia. We investigated the qualitative factors of memory that influence clinical and social status. METHODS: Psychosocial functioning, clinical symptoms, and memory function were assessed in 99 patients at four time points over a 16-month period using recall scores for semantically related words, unrelated words, paired associated learning, and word span. An initial cluster analysis using symptom assessment data from all four time points divided the sample into three groups: patients with low symptoms ratings that remained stable throughout the study period (low symptom-stable group - LSSG; N=51); patients with initially high symptoms ratings that subsequently improved (high symptom-improved group - HSIG; N=32); and patients with initially high symptoms ratings that deteriorated during the follow-up (high symptom-deteriorated group - HSDG; N=16). RESULTS: Memory was better preserved in LSSG compared to HSIG and HSDG patients. Recall performance was generally better for semantically related words than for unrelated words but the difference between LSSG and the two other groups was more constant over time for semantically related words. Extra-list errors variable was positively correlated with three PANSS measures (r=.25-.47). Also, the extra-list errors scores were correlated with the Magical Ideation Scale (r=.34-.39). Memory scores (global explicit, unrelated, related) were significantly and positively correlated with independent living skills (r=.26-.55) and the extra-list errors were negatively correlated with both social support and independent living skills (r=-.29 and r=-.46, respectively). All groups showed a reduction in extraneous false recognition errors/intrusions (FRIs) over time with the HSIG showing the greater change. HSIG and HSDG patients committed slightly more FRIs in recall tasks (extraneous information) than LSSG patients. CONCLUSION: Memory performance is better in patients presenting with less severe symptomatology. The extent to which FRIs reduce over time in patients with schizophrenia is a novel finding.