scieditor/keyword-auto-complete-corpus · Datasets at Hugging Face

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outcome number of panic attacks after 2 weeks of treatment two trials report the effects of propranolol 30 320 mg day versus benzodiazepines 1 30 mg day alprazolam or 5 40 mg day diazepam prescribed to adults with panic disorder with or without agoraphobia for a 2 week period expressed in mean number of panic attacks after 2 weeks of treatment noyes et al 1984 ravaris et al 1991
effect size for each study was expressed as a wmd
there was substantial statistical heterogeneity of studies two trials 50 participants in total χ2 3 04 df 1 p 0 08 i2 67
no significant difference was found between propranolol and benzodiazepines mean difference 1 58 95 ci 2 33 5 50 z 0 79 p 0 43 figure 3 a
meta analysis i propranolol versus benzodiazepines in panic disorder with or without agoraphobia outcome number of panic attacks after 2 weeks of treatment
meta analysis ii
outcome ham a after 2 weeks treatment two trials report the effects of propranolol 30 320 mg day versus benzodiazepines 1 30 mg day alprazolam or 5 40 mg day diazepam given to adults with panic disorder with or without agoraphobia for a 2 week period expressed in mean ham a after 2 weeks of treatment noyes et al 1984 ravaris et al 1991
wmds were calculated for continuous summary data obtained from the hamilton anxiety rating scale ham a a widely used scale to assess the severity of symptoms of anxiety hamilton 1959
there was substantial statistical heterogeneity of studies two trials 50 participants in total χ2 7 11 df 1 p 0 008 i2 86
no significant difference was found between propranolol and benzodiazepines mean difference 2 81 95 ci 16 87 22 49 z 0 28 p 0 78 figure 3 b
meta analysis ii
propranolol versus benzodiazepines in panic disorder with or without agoraphobia outcome ham a after 2 weeks treatment
meta analysis iii
outcome ham a after 2 6 weeks treatment three trials report the effects of propranolol 20 320 mg day versus benzodiazepines 0 5 30 mg day alprazolam or 5 40 mg day diazepam given to adults with panic disorder with or without agoraphobia for a 2 6 week period expressed in mean ham a scores at completion of treatment munjack et al 1989 noyes et al 1984 ravaris et al 1991
there was substantial statistical heterogeneity of studies three trials 92 participants in total χ2 7 74 df 2 p 0 02 i2 74
no significant overall effect was found mean difference 2 20 95 ci 8 49 4 09 z 0 99 p 0 32 figure 3 c
meta analysis iii
propranolol versus benzodiazepines in panic disorder with or without agoraphobia outcome ham a after 2 6 weeks treatment
meta analysis iv
outcome ham a after 6 weeks treatment two trials examined the effects of propranolol 30 300 mg day versus alprazolam 1 30 mg day given to adults with panic disorder with or without agoraphobia for a 2 week period expressed in mean ham a after 6 weeks of treatment munjack et al 1989 ravaris et al 1991
there was little statistical heterogeneity of studies two trials 68 participants in total χ2 1 14 df 1 p 0 29 i2 12
no significant difference was found between propranolol and alprazolam mean difference 0 51 95 ci 3 39 4 42 z 0 26 p 0 80 figure 3 d
meta analysis iv
propranolol versus alprazolam in panic disorder with or without agoraphobia outcome ham a after 6 weeks treatment
sensitivity analysis for one study included in all four meta analyses a high risk of selective outcome reporting was found ravaris et al 1991
the impact of this bias on the findings of our meta analyses was assessed
after excluding this study only one study remained for meta analyses i number of panic attacks after 2 weeks of treatment and meta analyses ii ham a after 2 weeks treatment noyes et al 1984 and one study remained for the meta analysis iv ham a after 6 weeks treatment munjack et al 1989
for the meta analysis iii ham a after 2 6 weeks treatment two studies remained munjack et al 1989 noyes et al 1984 of which the effects of compared treatment benzodiazepines and propranolol no longer reached statistical significance two trials 63 participants in total md 5 76 2 27 to 13 79 z 1 41 p 0 16 figure 3 e
sensitivity analysis
meta analysis iii with one study with high risk of selective outcome reporting included and excluded ravaris et al 1991
discussion this systematic review and meta analysis shows a lack of well designed clinical studies
this limits the scientific evidence and allows neither firm conclusions in favour or against the use of propranolol in the treatment of anxiety disorders nor recommendations for informed decision making in clinical practice
more specifically our meta analyses found no statistical difference between the effects of propranolol and benzodiazepines on anxiety and panic attack frequency munjack et al 1989 noyes et al 1984 ravaris et al 1991
in addition four moderate risk of bias trials failed to show solid evidence on the therapeutic effect of propranolol in patients with dental phobia liu et al 1991 animal type specific phobia fagerström et al 1985 and social phobia falloon et al 1981
no rcts were available on the effects of propranolol in the treatment of any of other anxiety disorders e g
generalised anxiety disorder obsessive compulsive disorder ocd separation anxiety disorder or selective mutism note that ptsd and ocd have been relocated to separate chapters in the dsm 5 american psychiatric association 2013
moreover despite widespread suggestions gardner 2010 giles 2005 lehrer 2012 no evidence was found for the effects of propranolol on ptsd symptom severity through inhibition of memory reconsolidation brunet et al 2008 or any other mechanism
to date statistical equivalence of the efficacy of propranolol versus benzodiazepines regarding the treatment of individuals with panic disorder with or panic disorder without agoraphobia has not been shown
because the evidence converges to suggest that propranolol and benzodiazepines prescribed in clinical settings have similar effectiveness in the short term treatment of these conditions munjack et al 1989 noyes et al 1984 ravaris et al 1991 other factors also need to be considered
first it takes time for an effect to become prominent upon administration
ssris generally require a period of 2 4 weeks while in some patients with panic disorder the onset of action may take up to 12 weeks michelson et al 2001 oehrberg et al 1995
therefore early adjuvant therapy with propranolol may be taken into consideration
second the side effects profile should be taken into account
whereas the clinical effects of benzodiazepines are considered equivalent to the first line pharmacotherapy of panic disorder ssris mitte 2005 roy byrne et al 2013 wilkinson et al 1991 they carry a high risk of unwanted sedative effects cognitive impairment and dependence and tolerance will develop over time baldwin et al 2014
conversely as compared with benzodiazepines the side effects of ssris are temporary reversible and relatively benign albeit still considerably frequent among others 10 gastrointestinal complaints fatigue insomnia and headache sandoz 2012
although side effects of propranolol occur less frequently among others 1 10 sleeping disturbances nightmares transient fatigue and cold extremities roy byrne et al 2013 sandoz 2012 the extent of the supporting evidence base is currently broader and more consistent for ssris than for propranolol otto et al 2001
therefore it would seem most reasonable not to divert from current treatment guidelines recommending ssris as the first line medication for panic disorder baldwin et al 2014 until robust data regarding the comparative efficacy and tolerability of propranolol versus ssris become available
with regard to the therapeutic effects of propranolol it has been proposed that propranolol s anxiolytic properties may result from its peripheral autonomic rather than its central activity balon et al 1990 clark 1986 roy byrne et al 2006
this may explain the lack of evidence for propranolol s efficacy in the long term treatment of anxiety disorders other than panic disorder
to this end it seems most likely that propranolol aids in breaking a vicious cycle of anxiety in which catastrophic misappraisal of bodily sensations of orthosympathetic origin such as palpitations or increased ventilation fuel the occurrence of panic attacks
this explanation is supported by research that found that subjects suffering from high levels of general trait anxiety improved little on propranolol becker 1976 kathol et al 1980 meibach et al 1987 wheatley 1969 whereas more favourable effects were found in the treatment of performance anxieties in which enhanced sensitivity for adrenergic hyperactivation may similarly initiate the fear response brantigan et al 1982 brewer 1972 clark and agras 1991 drew et al 1985 elman et al 1998 stone et al 1973
the present systematic review was limited by the moderate number of small studies examining the effects of propranolol on anxiety disorders and by the risk of bias these trials presented
notably the average loss to follow up was nearly one fifth of all participants
as withdrawal reasons were seldom reported the possibility of selective loss to follow up in some studies could not be ruled out
in conclusion the quality of evidence for the efficacy of propranolol at present is insufficient to support the routine use of propranolol in the treatment of any of the anxiety disorders
social cognition including emotion processing is a recognised deficit observed in patients with schizophrenia
it is one cognitive domain which has been emphasised as requiring further investigation with the efficacy of antipsychotic treatment on this deficit remaining unclear
nine studies met our criteria for entry into a meta analysis of the effects of medication on facial affect processing including data from 1162 patients and six antipsychotics
overall we found a small positive effect hedge s g 0 13 95 ci 0 05 to 0 21 p 0 002
in a subgroup analysis this was statistically significant for atypical but not typical antipsychotics
it should be noted that the pooled sample size of the typical subgroup was significantly lower than the atypical
meta regression analyses revealed that age gender and changes in symptom severity were not moderating factors
for the small positive effect on facial affect processing the clinical significance is questionable in terms of treating deficits in emotion identification in schizophrenia
we show that antipsychotic medications are poor at improving facial affect processing compared to reducing symptoms
this highlights the need for further investigation into the neuropharmacological mechanisms associated with accurate emotion processing to inform treatment options for these deficits in schizophrenia
introduction antipsychotic medication is used to treat positive symptoms in schizophrenia national institute for health and care excellence 2014
however deficits in social cognition have been shown to be strongly associated with functional outcome green et al 2004 and is one of eight domains identified by the initiative measurement and treatment research to improve cognition in schizophrenia matrics which require further investigation and treatment strategies nuechterlein et al 2004
in a review of the literature kucharska pietura and mortimer 2013 concluded that antipsychotics are unlikely to facilitate the recovery of social cognition deficits in schizophrenia based on a review of 15 articles
by far the most widely studied aspect of social cognition is emotion processing which is typically assessed using tasks requiring participants to perceive identify and discriminate between facial emotion expressions
a deficit in these abilities has consistently been found in schizophrenia kohler et al 2010
in a review specific to the facial affect recognition literature hempel and colleagues concluded based on eight studies that antipsychotic medication does not successfully treat this aspect of schizophrenia hempel et al 2010
while these reviews provide valuable descriptions of the relevant literature they are unable to provide a quantitative analysis of the effects of antipsychotic medication on these cognitive deficits
it also remains possible that the effects of treatment may be small or affected by moderating factors such as age gender or type of medication
in order to address these questions we have performed a meta analysis of studies specifically investigating the effects of antipsychotics on emotion processing in schizophrenia
methods a literature search was carried out using pubmed and web of knowledge databases entering the search terms schizophrenia and facial and emotion and antipsychotic in may 2014
in addition a manual search was carried out in reference sections of papers returned
we included english language studies that a used a task investigating facial emotion processing b specifically investigated the effects of antipsychotic medication c provided pre and post medication data and d included patients with a diagnosis of schizophrenia
nine studies met these inclusion criteria confirmed by two of the authors asg and mam see figure 1
flowchart showing study selection for the meta analysis
methods studies employed a range of tasks with the predominant outcome measure being number of correct incorrect responses n 8
the outcome measure from one study cabral calderin et al 2010 was number of phases of facial morphing before a correct response
where data were not available in an appropriate form authors were contacted requesting additional information
for studies investigating multiple antipsychotics each drug was entered into the meta analysis separately
these were independent samples
hedge s g and its 95 confidence intervals ci were calculated for each study and each drug
hedge s g is a measure of effect size similar to cohen s d but corrected for small sample size ellis 2010
a random effects meta analysis subgrouped by typical and atypical antipsychotics was carried out using review manager 5 2 the nordic cochrane centre 2012 using an inverse variance weighted model
between study heterogeneity was assessed using the i2 statistic
egger s intercept and visual inspection of funnel plots was used to assess evidence of publication bias egger et al 1997
we also carried out meta regression analyses using the metareg module in stata statistical software harbord and higgins 2008 statacorp 2011 to assess the influence of symptoms age and gender on task performance
one study cabral calderin et al 2010 reported subscales of tasks with no overall score
the total score and standard deviation sd for these subscales were calculated using an estimation of the correlation coefficient between subscales as 0 8 in order to sum the sds
sensitivity analyses were carried out to determine if altering this estimation affected the pooled effect size
literature search after 57 duplicates were removed 84 studies were returned by the original search
of these nine studies met the inclusion criteria investigating six antipsychotics haloperidol perphenazine perazine riseridone quetiapine olanzapine bediou et al 2007 behere et al 2009 cabral calderin et al 2010 daros et al 2014 harvey et al 2006 lewis and garver 1995 penn et al 2009 sergi et al 2007 wölwer et al 1996 in 1152 patients with schizophrenia see table 1 for study details
overall there was no bias with regard to which emotions were examined
two studies daros et al 2014 harvey et al 2006 only focused on two emotions the range of intensity from very happy to very sad four studies behere et al 2009 cabral calderin et al 2010 lewis and garver 1995 wölwer et al 1996 investigated processing of happiness disgust sadness surprise anger and fearful expressions one study bediou et al 2007 investigated processing of neutral happiness disgust fear and anger two studies investigated processing of happiness sadness anger surprise fear and shame penn et al 2009 sergi et al 2007
details of included studies
p pre post design d drug free baseline r randomised w washout drug cross over period db double blind fd fixed dose fl flexible dose far facial affect recognition ekman and friesen 1976 efer emotional facial expression recognition feit facial emotion identification test photos developed by izard 1971 and ekman and friesen 1976 trends tool for recognition of emotions in neuropsychiatric disorders behere 2009 peat penn emotional acuity test cornblatt 1989 fedt face emotion discrimination test kerr and neale 1993 eemt emotional expression multimorph task mendoza 2011 cpze chlorpromazine equivalents bprs brief psychiatric rating scale sans scale for the assessment for negative symptoms saps scale for the assessment for positive symptoms panss positive and negative syndrome scale
overall meta analysis the overall pooled hedge s g was 0 13 95 ci 0 05 to 0 21 p 0 002 see figure 2

outcome number of panic attacks after 2 weeks of treatment two trials report the effects of propranolol 30 320 mg day versus benzodiazepines 1 30 mg day alprazolam or 5 40 mg day diazepam prescribed to adults with panic disorder with or without agoraphobia for a 2 week period expressed in mean number of panic attacks after 2 weeks of treatment noyes et al 1984 ravaris et al 1991

effect size for each study was expressed as a wmd

there was substantial statistical heterogeneity of studies two trials 50 participants in total χ2 3 04 df 1 p 0 08 i2 67

no significant difference was found between propranolol and benzodiazepines mean difference 1 58 95 ci 2 33 5 50 z 0 79 p 0 43 figure 3 a

meta analysis i propranolol versus benzodiazepines in panic disorder with or without agoraphobia outcome number of panic attacks after 2 weeks of treatment

meta analysis ii

outcome ham a after 2 weeks treatment two trials report the effects of propranolol 30 320 mg day versus benzodiazepines 1 30 mg day alprazolam or 5 40 mg day diazepam given to adults with panic disorder with or without agoraphobia for a 2 week period expressed in mean ham a after 2 weeks of treatment noyes et al 1984 ravaris et al 1991

wmds were calculated for continuous summary data obtained from the hamilton anxiety rating scale ham a a widely used scale to assess the severity of symptoms of anxiety hamilton 1959

there was substantial statistical heterogeneity of studies two trials 50 participants in total χ2 7 11 df 1 p 0 008 i2 86

no significant difference was found between propranolol and benzodiazepines mean difference 2 81 95 ci 16 87 22 49 z 0 28 p 0 78 figure 3 b

meta analysis ii

propranolol versus benzodiazepines in panic disorder with or without agoraphobia outcome ham a after 2 weeks treatment

meta analysis iii

outcome ham a after 2 6 weeks treatment three trials report the effects of propranolol 20 320 mg day versus benzodiazepines 0 5 30 mg day alprazolam or 5 40 mg day diazepam given to adults with panic disorder with or without agoraphobia for a 2 6 week period expressed in mean ham a scores at completion of treatment munjack et al 1989 noyes et al 1984 ravaris et al 1991

there was substantial statistical heterogeneity of studies three trials 92 participants in total χ2 7 74 df 2 p 0 02 i2 74

no significant overall effect was found mean difference 2 20 95 ci 8 49 4 09 z 0 99 p 0 32 figure 3 c

meta analysis iii

propranolol versus benzodiazepines in panic disorder with or without agoraphobia outcome ham a after 2 6 weeks treatment

meta analysis iv

outcome ham a after 6 weeks treatment two trials examined the effects of propranolol 30 300 mg day versus alprazolam 1 30 mg day given to adults with panic disorder with or without agoraphobia for a 2 week period expressed in mean ham a after 6 weeks of treatment munjack et al 1989 ravaris et al 1991

there was little statistical heterogeneity of studies two trials 68 participants in total χ2 1 14 df 1 p 0 29 i2 12

no significant difference was found between propranolol and alprazolam mean difference 0 51 95 ci 3 39 4 42 z 0 26 p 0 80 figure 3 d

meta analysis iv

propranolol versus alprazolam in panic disorder with or without agoraphobia outcome ham a after 6 weeks treatment

sensitivity analysis for one study included in all four meta analyses a high risk of selective outcome reporting was found ravaris et al 1991

the impact of this bias on the findings of our meta analyses was assessed

after excluding this study only one study remained for meta analyses i number of panic attacks after 2 weeks of treatment and meta analyses ii ham a after 2 weeks treatment noyes et al 1984 and one study remained for the meta analysis iv ham a after 6 weeks treatment munjack et al 1989

for the meta analysis iii ham a after 2 6 weeks treatment two studies remained munjack et al 1989 noyes et al 1984 of which the effects of compared treatment benzodiazepines and propranolol no longer reached statistical significance two trials 63 participants in total md 5 76 2 27 to 13 79 z 1 41 p 0 16 figure 3 e

sensitivity analysis

meta analysis iii with one study with high risk of selective outcome reporting included and excluded ravaris et al 1991

discussion this systematic review and meta analysis shows a lack of well designed clinical studies

this limits the scientific evidence and allows neither firm conclusions in favour or against the use of propranolol in the treatment of anxiety disorders nor recommendations for informed decision making in clinical practice

more specifically our meta analyses found no statistical difference between the effects of propranolol and benzodiazepines on anxiety and panic attack frequency munjack et al 1989 noyes et al 1984 ravaris et al 1991

in addition four moderate risk of bias trials failed to show solid evidence on the therapeutic effect of propranolol in patients with dental phobia liu et al 1991 animal type specific phobia fagerström et al 1985 and social phobia falloon et al 1981

no rcts were available on the effects of propranolol in the treatment of any of other anxiety disorders e g

generalised anxiety disorder obsessive compulsive disorder ocd separation anxiety disorder or selective mutism note that ptsd and ocd have been relocated to separate chapters in the dsm 5 american psychiatric association 2013

moreover despite widespread suggestions gardner 2010 giles 2005 lehrer 2012 no evidence was found for the effects of propranolol on ptsd symptom severity through inhibition of memory reconsolidation brunet et al 2008 or any other mechanism

to date statistical equivalence of the efficacy of propranolol versus benzodiazepines regarding the treatment of individuals with panic disorder with or panic disorder without agoraphobia has not been shown

because the evidence converges to suggest that propranolol and benzodiazepines prescribed in clinical settings have similar effectiveness in the short term treatment of these conditions munjack et al 1989 noyes et al 1984 ravaris et al 1991 other factors also need to be considered

first it takes time for an effect to become prominent upon administration

ssris generally require a period of 2 4 weeks while in some patients with panic disorder the onset of action may take up to 12 weeks michelson et al 2001 oehrberg et al 1995

therefore early adjuvant therapy with propranolol may be taken into consideration

second the side effects profile should be taken into account

whereas the clinical effects of benzodiazepines are considered equivalent to the first line pharmacotherapy of panic disorder ssris mitte 2005 roy byrne et al 2013 wilkinson et al 1991 they carry a high risk of unwanted sedative effects cognitive impairment and dependence and tolerance will develop over time baldwin et al 2014

conversely as compared with benzodiazepines the side effects of ssris are temporary reversible and relatively benign albeit still considerably frequent among others 10 gastrointestinal complaints fatigue insomnia and headache sandoz 2012

although side effects of propranolol occur less frequently among others 1 10 sleeping disturbances nightmares transient fatigue and cold extremities roy byrne et al 2013 sandoz 2012 the extent of the supporting evidence base is currently broader and more consistent for ssris than for propranolol otto et al 2001

therefore it would seem most reasonable not to divert from current treatment guidelines recommending ssris as the first line medication for panic disorder baldwin et al 2014 until robust data regarding the comparative efficacy and tolerability of propranolol versus ssris become available

with regard to the therapeutic effects of propranolol it has been proposed that propranolol s anxiolytic properties may result from its peripheral autonomic rather than its central activity balon et al 1990 clark 1986 roy byrne et al 2006

this may explain the lack of evidence for propranolol s efficacy in the long term treatment of anxiety disorders other than panic disorder

to this end it seems most likely that propranolol aids in breaking a vicious cycle of anxiety in which catastrophic misappraisal of bodily sensations of orthosympathetic origin such as palpitations or increased ventilation fuel the occurrence of panic attacks

this explanation is supported by research that found that subjects suffering from high levels of general trait anxiety improved little on propranolol becker 1976 kathol et al 1980 meibach et al 1987 wheatley 1969 whereas more favourable effects were found in the treatment of performance anxieties in which enhanced sensitivity for adrenergic hyperactivation may similarly initiate the fear response brantigan et al 1982 brewer 1972 clark and agras 1991 drew et al 1985 elman et al 1998 stone et al 1973

the present systematic review was limited by the moderate number of small studies examining the effects of propranolol on anxiety disorders and by the risk of bias these trials presented

notably the average loss to follow up was nearly one fifth of all participants

as withdrawal reasons were seldom reported the possibility of selective loss to follow up in some studies could not be ruled out

in conclusion the quality of evidence for the efficacy of propranolol at present is insufficient to support the routine use of propranolol in the treatment of any of the anxiety disorders

social cognition including emotion processing is a recognised deficit observed in patients with schizophrenia

it is one cognitive domain which has been emphasised as requiring further investigation with the efficacy of antipsychotic treatment on this deficit remaining unclear

nine studies met our criteria for entry into a meta analysis of the effects of medication on facial affect processing including data from 1162 patients and six antipsychotics

overall we found a small positive effect hedge s g 0 13 95 ci 0 05 to 0 21 p 0 002

in a subgroup analysis this was statistically significant for atypical but not typical antipsychotics

it should be noted that the pooled sample size of the typical subgroup was significantly lower than the atypical

meta regression analyses revealed that age gender and changes in symptom severity were not moderating factors

for the small positive effect on facial affect processing the clinical significance is questionable in terms of treating deficits in emotion identification in schizophrenia

we show that antipsychotic medications are poor at improving facial affect processing compared to reducing symptoms

this highlights the need for further investigation into the neuropharmacological mechanisms associated with accurate emotion processing to inform treatment options for these deficits in schizophrenia

introduction antipsychotic medication is used to treat positive symptoms in schizophrenia national institute for health and care excellence 2014

however deficits in social cognition have been shown to be strongly associated with functional outcome green et al 2004 and is one of eight domains identified by the initiative measurement and treatment research to improve cognition in schizophrenia matrics which require further investigation and treatment strategies nuechterlein et al 2004

in a review of the literature kucharska pietura and mortimer 2013 concluded that antipsychotics are unlikely to facilitate the recovery of social cognition deficits in schizophrenia based on a review of 15 articles

by far the most widely studied aspect of social cognition is emotion processing which is typically assessed using tasks requiring participants to perceive identify and discriminate between facial emotion expressions

a deficit in these abilities has consistently been found in schizophrenia kohler et al 2010

in a review specific to the facial affect recognition literature hempel and colleagues concluded based on eight studies that antipsychotic medication does not successfully treat this aspect of schizophrenia hempel et al 2010

while these reviews provide valuable descriptions of the relevant literature they are unable to provide a quantitative analysis of the effects of antipsychotic medication on these cognitive deficits

it also remains possible that the effects of treatment may be small or affected by moderating factors such as age gender or type of medication

in order to address these questions we have performed a meta analysis of studies specifically investigating the effects of antipsychotics on emotion processing in schizophrenia

methods a literature search was carried out using pubmed and web of knowledge databases entering the search terms schizophrenia and facial and emotion and antipsychotic in may 2014

in addition a manual search was carried out in reference sections of papers returned

we included english language studies that a used a task investigating facial emotion processing b specifically investigated the effects of antipsychotic medication c provided pre and post medication data and d included patients with a diagnosis of schizophrenia

nine studies met these inclusion criteria confirmed by two of the authors asg and mam see figure 1

flowchart showing study selection for the meta analysis

methods studies employed a range of tasks with the predominant outcome measure being number of correct incorrect responses n 8

the outcome measure from one study cabral calderin et al 2010 was number of phases of facial morphing before a correct response

where data were not available in an appropriate form authors were contacted requesting additional information

for studies investigating multiple antipsychotics each drug was entered into the meta analysis separately

these were independent samples

hedge s g and its 95 confidence intervals ci were calculated for each study and each drug

hedge s g is a measure of effect size similar to cohen s d but corrected for small sample size ellis 2010

a random effects meta analysis subgrouped by typical and atypical antipsychotics was carried out using review manager 5 2 the nordic cochrane centre 2012 using an inverse variance weighted model

between study heterogeneity was assessed using the i2 statistic

egger s intercept and visual inspection of funnel plots was used to assess evidence of publication bias egger et al 1997

we also carried out meta regression analyses using the metareg module in stata statistical software harbord and higgins 2008 statacorp 2011 to assess the influence of symptoms age and gender on task performance

one study cabral calderin et al 2010 reported subscales of tasks with no overall score

the total score and standard deviation sd for these subscales were calculated using an estimation of the correlation coefficient between subscales as 0 8 in order to sum the sds

sensitivity analyses were carried out to determine if altering this estimation affected the pooled effect size

literature search after 57 duplicates were removed 84 studies were returned by the original search

of these nine studies met the inclusion criteria investigating six antipsychotics haloperidol perphenazine perazine riseridone quetiapine olanzapine bediou et al 2007 behere et al 2009 cabral calderin et al 2010 daros et al 2014 harvey et al 2006 lewis and garver 1995 penn et al 2009 sergi et al 2007 wölwer et al 1996 in 1152 patients with schizophrenia see table 1 for study details

overall there was no bias with regard to which emotions were examined

two studies daros et al 2014 harvey et al 2006 only focused on two emotions the range of intensity from very happy to very sad four studies behere et al 2009 cabral calderin et al 2010 lewis and garver 1995 wölwer et al 1996 investigated processing of happiness disgust sadness surprise anger and fearful expressions one study bediou et al 2007 investigated processing of neutral happiness disgust fear and anger two studies investigated processing of happiness sadness anger surprise fear and shame penn et al 2009 sergi et al 2007

details of included studies

p pre post design d drug free baseline r randomised w washout drug cross over period db double blind fd fixed dose fl flexible dose far facial affect recognition ekman and friesen 1976 efer emotional facial expression recognition feit facial emotion identification test photos developed by izard 1971 and ekman and friesen 1976 trends tool for recognition of emotions in neuropsychiatric disorders behere 2009 peat penn emotional acuity test cornblatt 1989 fedt face emotion discrimination test kerr and neale 1993 eemt emotional expression multimorph task mendoza 2011 cpze chlorpromazine equivalents bprs brief psychiatric rating scale sans scale for the assessment for negative symptoms saps scale for the assessment for positive symptoms panss positive and negative syndrome scale

overall meta analysis the overall pooled hedge s g was 0 13 95 ci 0 05 to 0 21 p 0 002 see figure 2