Negative symptoms in schizophrenia: considerations for clinical trials

Möller, Hans‐Jürgen; Praag, H. M. van; B, Aufdembrinke; Bailey, Paul; Barnes, Thomas R. E.; Beck, Jamie; Bentsen, Håvard; Eich, F.X.; Farrow, L.R.; Fleischhacker, W. W.; Gerlach, Jes; Grafford, Kerstin; Hentschel, Bettina; Hertkorn, A.; Heylen, S; Lecrubier, Y.; Leonard, J. P.; McKenna, Peter J.; Maier, Wolfgang; Pedersen, V.; Rappard, A.; Rein, W.; Ryan, James; Nielsen, M S; Stieglitz, R. D.; Wegener, Gregers; Wilson, James E.

doi:10.1007/bf02244775

Cited by 65 publications

(19 citation statements)

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“…The symptoms of schizophrenia are classiÞed as positive or negative, and the e¤ects of antipsychotics di¤er between these two types of symptoms (Moller 1994). Atypical neuroleptics have been reported to act on DA subtype (Sokolo¤ et al 1990;Seeman et al 1993), 5-HT (Bleich et al 1988), NMDA (Carlsson and Carlsson 1990;Javitt et al 1991;Nishikawa 1993), and r receptors (Deutsch et al 1988), so information concerning DA receptors alone is not su¦cient to assess the potential e¦cacy of drugs for schizophrenia.…”

Section: Introductionsupporting

confidence: 43%

Cortical and hippocampal EEG power spectra in animal models of schizophrenia produced with methamphetamine, cocaine, and phencyclidine

Yamamoto

1997

Psychopharmacology

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Cortical and hippocampal EEGs in animal models of schizophrenia were compared to those obtained with psychotomimetics or antipsychotic agents by utilizing power spectral analysis. Models of positive schizophrenic symptoms were created with methamphetamine (MAP) and cocaine, and a model of both negative and positive symptoms was created with PCP. MAP caused a prolonged decrease in the cortical EEG power spectra, cocaine caused a marked decrease for a short time, and PCP produced no significant changes. In the hippocampal spectra, MAP induced a marked increase in the T2(6.0-7.9 Hz)/ T1(4.0-5.9 Hz) ratio, PCP caused a decrease of this ratio after an initial increase, and cocaine produced no significant change. (An increase in the T2/T1 ratio represents a shift of theta waves to higher frequencies.) Since apomorphine (a DA agonist) and MK-801 (an NMDA antagonist) caused the T2/T1 ratio to increase, positive schizophrenic symptoms caused by MAP may be related to the DA and NMDA systems. 3-PPP (a sigma agonist) caused biphasic changes similar to those induced by PCP. Haloperidol and chlorpromazine caused a decrease of the T2/T1 ratio. These results indicate that cortical and hippocampal EEG power spectra (especially the hippocampal T2/T1 ratio) can be used to characterize both qualitatively and quantitatively models of schizophrenia.

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Section: Introductionsupporting

confidence: 43%

Cortical and hippocampal EEG power spectra in animal models of schizophrenia produced with methamphetamine, cocaine, and phencyclidine

Yamamoto

1997

Psychopharmacology

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“…However, the only statistically signiÞcant di¤erence from placebo was in the mean change in the BPRS anergia factor score in the ziprasidone 120 mg / day group. The lack of any statistically signiÞcant di¤erence between ziprasidone 120 mg / day and placebo on the SANS may be due to the short duration of the trial and the confound associated with studying negative symptoms in acutely ill patients (Möller et al 1994;Möller 1995;King 1998). Evidence of e¦cacy in the treatment of negative symptoms has been demonstrated in a 6-week clinical trial of patients with an acute exacerbation of schizophrenia or schizoa¤ective disorder where both ziprasidone 80 and 160 mg / day were signiÞcantly more e¤ective than placebo in reducing PANSS negative symptom subscale scores (Reeves and Harrigan 1996).…”

Section: Discussionmentioning

confidence: 47%

Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial

et al. 1998

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A double-blind, placebo-controlled, multicenter study, was performed to evaluate the efficacy and safety of ziprasidone in 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder. Patients were randomized to receive ziprasidone 40 mg/day, 120 mg/day or placebo for 28 days. Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total, CGI-S. BPRS depression cluster and BPRS anergia cluster scores (all P < 0.05). Similarly, the percentages of patients classified as responders on the BPRS (> or = 30% reduction) and the CGI improvement (score < or = 2) were significantly greater with ziprasidone 120 mg/day compared with placebo (P < 0.05). The number of patients who experienced an adverse event was similar in all three treatment groups, and discontinuation due to adverse events was rare (five of 91 ziprasidone-treated patients). The most frequently reported adverse events, that were more common in either ziprasidone group than in the placebo group, were dyspepsia, constipation, nausea and abdominal pain. There was a notably low incidence extrapyramidal side-effects (including akathisia) and postural hypotension and no pattern of laboratory abnormalities or apparent weight gain. Ziprasidone-treated patients were not clinically different from placebo-treated patients on the Simpson-Angus Rating scale, Barnes Akathisia scale and AIMS assessments. These results indicate that ziprasidone 120 mg/day is effective in the treatment of the positive, negative and affective symptoms of schizophrenia and schizoaffective disorder with a very low side-effect burden.

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“…In the clinical arena, amisulpride in low doses (100 mg per day) was compared with placebo, double blind, in a large randomized trial29 which met criteria for valid evaluation 30. Patients had high levels of negative symptoms, and a DSM-III-R diagnosis of residual schizophrenia.…”

Section: Amisulpride For Negative Symptomsmentioning

confidence: 99%

Update on the management of symptoms in schizophrenia: focus on amisulpride

Mortimer¹

2009

NDT

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Amisulpride is an atypical antipsychotic drug with a unique receptor pharmacology which is dose dependent. It is a standard treatment in dysthymia as well as in psychosis. Amisulpride is efficacious, effective and well tolerated in positive symptoms of schizophrenia: there is extensive evidence that it treats negative symptoms when given in low doses, although relative lack of EPS and an antidepressant effect may contribute. In first-episode patients amisulpride is an option, although there is little comparative work available. Amisulpride has the best evidence as an effective adjunct to clozapine treatment. Regarding intellectual function, amisulpride appears cognitive sparing but the clinical relevance of this remains obscure. There is evidence that amisulpride can improve social function but again there is little comparative work to demonstrate any particular advantages. Regarding the current conventional versus atypical antipsychotic controversy, amisulpride did better in switching studies and meta-analyses than in the single large pragmatic randomized trial reported to date. It is a versatile drug, and may offer advantages over other atypical antipsychotic drugs in the treatment of negative and depressive symptoms, and tolerability advantages such as the avoidance of weight gain. Essentially it rests with the treating clinician to employ a rational psychopharmacological approach towards the individual patient: there will be few circumstances in which amisulpride will not be a likely contender as a treatment choice.

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Negative symptoms in schizophrenia: considerations for clinical trials

Cited by 65 publications

References 65 publications

Cortical and hippocampal EEG power spectra in animal models of schizophrenia produced with methamphetamine, cocaine, and phencyclidine

Cortical and hippocampal EEG power spectra in animal models of schizophrenia produced with methamphetamine, cocaine, and phencyclidine

Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial

Update on the management of symptoms in schizophrenia: focus on amisulpride

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