Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: a double-blind placebo-controlled study

Abstract

Despite the availability of atypical antipsychotics, the treatment of negative symptoms in schizophrenia remains a challenge. This study was designed to confirm the positive effect observed in our pilot study with paroxetine as augmentation to antipsychotics in the treatment of negative symptoms in chronic schizophrenia. Twenty-nine patients with chronic schizophrenia, as defined by DSM-IV, who scored at least 20 points on the negative subscale of the Positive and Negative Syndrome Scale (PANSS) were randomized for treatment with 30 mg paroxetine or placebo in a double-blind, placebo-controlled study for 12 weeks. Ratings included the PANSS, the Hamilton Rating Scale for Depression (HAM-D) and scales for extrapyramidal side-effects. An intention-to-treat analysis was based on the 25 patients who were available for at least one follow-up assessment. The last observation carried forward principle was applied. The mean score of the negative subscale of the PANSS decreased in both groups. Using an analysis of covariance, there was a significant treatment effect with paroxetine compared to placebo with respect to negative symptoms (-4.53; 95% confidence interval -9.054 to -0.015). The mean HAM-D scores remained almost constant. The study suggests the efficacy of paroxetine with respect to the treatment of negative symptoms in chronic schizophrenia.

When GWAS meets the Connectivity Map: drug repositioning for seven psychiatric disorders

“…Some top candidates have been shown to improve negative symptoms in clinical studies, such as the H 2 antagonist ranitidine 39 and the alpha 2 receptor antagonist idazoxan 40 . The antidepressant paroxetine was also tested in a double-blind clinical trial and shown to be efficacious in ameliorating negative symptoms in schizophrenia 41 . There are other drug candidate with preliminary support by preclinical or clinical studies with diverse mechanisms, such as the serotonin and dopamine antagonist metitepine 42 , the Na-K-Cl cotransporter 1 inhibitor bumetanide 43 and the non-steroidal anti-inflammatory drug (NSAID) meclofenamic acid 44 .…”

Elderly patients with very late-onset schizophrenia-like psychosis and early-onset schizophrenia: Cross-sectional and retrospective clinical findings

“…These residual symptoms might also be explained by a lesser efficacy of neuroleptics to control negative symptoms [41]. It is also possible that some symptoms such as reduced facial expression and energy might be extrapyramidal side effects of the medication rather than intrinsic negative symptoms [42].…”

Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial

“…[33][34][35] Clinical trials have provided evidence that the combined administration of an antipsychotic drug and an 'add-on' SSRI -such as fluoxetine, fluvoxamine, paroxetine or citalopram -can improve negative symptoms and some affective disorders associated with schizophrenia, without exacerbating extrapyramidal side effects, in patients in whom such problems have proved persistent and who have been, being unresponsive to antipsychotic monotherapy. [36][37][38][39][40][41] For example, the efficacy and safety of paroxetine augmentation has been demonstrated in small pilot studies 42 and a double-blind placebo-controlled study. 41 Fluvoxamine and fluoxetine have also shown some beneficial effects in placebo-controlled, double-blind studies, 36,38,43 in particular, fluvoxamine improved affective blunting.…”

“…[36][37][38][39][40][41] For example, the efficacy and safety of paroxetine augmentation has been demonstrated in small pilot studies 42 and a double-blind placebo-controlled study. 41 Fluvoxamine and fluoxetine have also shown some beneficial effects in placebo-controlled, double-blind studies, 36,38,43 in particular, fluvoxamine improved affective blunting. Fluoxetine in combination with a depot antipsychotic caused an overall improvement in negative symptoms, 38 although it failed to do so in combination with clozapine.…”

“…The first participant was recruited in September 2011 and recruitment finished at the end of September 2013. The participants were people under the care of secondary mental health services, with an established schizophrenic illness characterised by persistent negative symptoms at a criterion level of severity, despite treatment with antipsychotic medication: a negative subscale score of 20 or more 41,94,95 on the PANSS with at least three of the seven items on the negative symptom subscale rated ≥ 3. Eligibility for the study was determined by the following, additional, inclusion and exclusion criteria.…”