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Attitudes towards and rationale for antipsychotic polypharmacy among psychiatrists in Nigeria: Characteristics associated with high reported antipsychotic polypharmacy
Psychiatry Research 248 (2017) 134–139
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Attitudes towards and rationale for antipsychotic polypharmacy among psychiatrists in Nigeria: Characteristics associated with high reported antipsychotic polypharmacy
MARK
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B.O. Jamesa, , J.O. Omoaregbaa, S.O. Rajia, O.E. Imishueb, K.M. Okonodac,i, Y.I. Nyamalid, P.A. Famuyiwae, C.U. Correllf,g,h a
Department of Clinical Services, Federal Neuro-Psychiatric Hospital, Benin-City, Nigeria Department of Clinical Services, Neuro-Psychiatric Hospital, Aro, Abeokuta, Nigeria Department of Psychiatry, University of Jos, Jos, Plateau State, Nigeria d Department of Clinical Services, Federal Neuro-Psychiatric Hospital, Yaba, Lagos, Nigeria e Department of Clinical Services, Federal Neuro-Psychiatric Hospital, Calabar, Cross River, Nigeria f The Zucker Hillside Hospital, Psychiatry Research, Northwell Health System, Glen Oaks, NY, USA g Hofstra Northwell School of Medicine, Hempstead, NY, USA h The Feinstein Institute for Medical Research, Manhasset, NY, USA i Jos University Teaching Hospital, Jos, Plateau State, Nigeria b c
A R T I C L E I N F O
A BS T RAC T
Keywords: Antipsychotic polypharmacy Rationale Reasons Survey Psychiatrists Nigeria
Antipsychotic polypharmacy (APP) is commonplace despite lacking evidence of its effectiveness. We aimed to identify psychiatrists’ rationale for and attitudes towards APP and to determine if attitudes influence antipsychotic polypharmacy prescription rates in a survey of a nationally representative sample of Nigerian psychiatrists (of which a majority were senior trainees: 74.2%). Prescriber characteristics, practices and attitudes were compared in ‘high’ ( > 30%) vs. ‘low’ (≤30%) antipsychotic polypharmacy prescribers and results were adjusted for multiple comparisons. Altogether, prescribers reported utilizing antipsychotic polypharmacy in 36.2% of their patients. Compared to ‘low’ antipsychotic polypharmacy prescribers, ‘high’ prescribers were significantly more likely using first-generation antipsychotics (FGA) combination, to have attempted a switch to monotherapy in less patients, or been successful in doing so. ‘High’ and ‘low’ antipsychotic polypharmacy prescribers were equally moderately concerned about the effects of antipsychotic polypharmacy and also did not differ regarding reasons not justifying antipsychotic polypharmacy. In a multivariable, backward elimination logistic regression model, ‘low’ antipsychotic polypharmacy was associated with having successfully switched patients to monotherapy, whereas the ‘high’ antipsychotic polypharmacy was associated with preferring FGA +FGA combinations and aiming for a reduction of non-antipsychotic medications. Antipsychotic polypharmacy is common among psychiatrists in Nigeria, with ‘high’ and ‘low’ antipsychotic polypharmacy prescribers sharing similar concerns/attitudes, but differing regarding their primary aim for antipsychotic polypharmacy and in their specific antipsychotic polypharmacy use characteristics.
1. Introduction Antipsychotic polypharmacy is common in psychiatric practice (Correll et al., 2011; Kishimoto et al., 2013). Rates of antipsychotic polypharmacy vary around the world (Gallego et al., 2012a; Li et al., 2015), and antipsychotic polypharmacy is associated with higher antipsychotic doses and more frequent adverse effects related to dopamine blockade as well as greater anticholinergic medication use (Adesola et al., 2013; Correll and Gallego, 2012; Gallego et al., 2012b;
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Koen et al., 2008). Due to lacking evidence for the efficacy and safety of antipsychotic polypharmacy (Barbui et al., 2009; Correll et al., 2009; Gallego et al., 2012b; Lochmann van Bennekom et al., 2013; Taylor et al., 2012)., clinical guidelines recommend antipsychotic monotherapy, especially in the acute phases of schizophrenia-related illnesses, recommending also clozapine and not antipsychotic polypharmacy for treatment resistant patients (Falkai et al., 2009). Despite these guidelines and insufficient database supporting its use, antipsychotic polypharmacy has remained common among clients receiving antipsychotic
Corresponding author. E-mail address: [email protected] (B.O. James).
http://dx.doi.org/10.1016/j.psychres.2016.12.032 Received 29 February 2016; Received in revised form 29 October 2016; Accepted 24 December 2016 Available online 27 December 2016 0165-1781/ © 2016 Elsevier Ireland Ltd. All rights reserved.
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medications (Chang and Kim, 2014; Gallego et al., 2012a). Given the absence of convincing data supporting its use antipsychotic polypharmacy, is reflective of the practice-based prescribing preferences of psychiatrists who may have a clinical rationale for instituting and maintaining antipsychotic polypharmacy for certain patient subgroups and under specific conditions. Individualized clinical decision making as an underlying reason for antipsychotic polypharmacy is also indicated by wide practice and regional variations in antipsychotic polypharmacy frequency in surveys conducted at the same time and in the same country and health care setting (Correll and Gallego, 2012; Correll et al., 2011). A disconnect between evidence and guidelines on the one hand and clinical practice on the other makes it pertinent to understand reasons for attitudes towards and characteristics of antipsychotic polypharmacy from the practitioners’ perspective. The complexity of this clinical practice example is exemplified by the fact that some studies have indicated that, at least, in some clinical situations antipsychotic polypharmacy may be associated with better treatment response (Correll et al., 2009) or quality of life (Li et al., 2014). Furthermore, antipsychotic polypharmacy may be attempted after observed “inefficacy” of just one antipsychotic trials and despite low dose monotherapy treatment in almost half of those patients (Tsutsumi et al., 2011). On the other hand, antipsychotic polypharmacy has also been associated with a greater number of some side effects (Gallego et al., 2012b; Li et al., 2015), yet other side effects may be reduced, especially when adding a partial D2 agonist to a full D2 antagonist (Gallego et al., 2012b). Reports on practitioners’ perspectives on antipsychotic polypharmacy to better understand antipsychotic polypharmacy decision making and practice have been few and have largely been undertaken in North America, Europe and Asia (Correll et al., 2011; Kishimoto et al., 2013; Ito et al., 2005; Sernyak and Rosenheck, 2004; IasevoLi et al., 2014). This study, therefore, sought to ascertain the reported prevalence of antipsychotic polypharmacy among psychiatrists in Nigeria as well as to identify reasons for and correlates of prescribing patterns of antipsychotic polypharmacy using a self-administered, semi-structured questionnaire that has been used previously for the same purpose (Correll et al., 2011; Kishimoto et al., 2013).
self-reported, estimated percentage of patients on antipsychotic polypharmacy; preferred antipsychotic combination(s); estimated percentage of patients in whom conversion to antipsychotic monotherapy was attempted and if it was successful or unsuccessful; how much prescribers globally feel that antipsychotic polypharmacy is problematic (using a 7-point Likert scale: 1=not at all, 2=minimal, 3=mild, 4=moderate, 5=marked, 6=severe, 7=extreme); as well as attitudes regarding specific reasons for and reasons against antipsychotic polypharmacy (using a 5-point Likert scale assessing the degree by which prescribers felt antipsychotic polypharmacy was or was not justified based on provided characteristics: 1= not at all (=0%) 2=a little bit (=25%), 3=somewhat (=50%), 4=a lot (=75%), 5=a whole lot (100% justified) (Kishimoto et al., 2013).
2.3. Ethical considerations All participating prescribers were assured of complete confidentiality and anonymity. No identifying information was obtained, and participants were free to decline to participate in or opt out of this research study. Each questionnaire contained an information sheet, and participants were deemed to have provided informed consent when they read and proceeded to complete the questionnaire.
2.4. Data analysis Data were analysed using the Statistical Package for Social Sciences (SPSS) Software version 20 (SPSS Inc.). Data were summarized using descriptive statistics. Prescriber characteristics, practices and attitudes were compared in ‘high’ ( > 30%) vs. ‘low’ (≤30%) antipsychotic polypharmacy prescribers, using the median split of 30% as done in the previous two studies using the PRACT-Q (Correll et al., 2011; Kishimoto et al., 2013). Bivariate categorical comparisons were performed using the chi-squared test while for continuous data, normally distributed data were compared using the Students’ t-test, and nonnormally distributed data compared using Mann-Whitney U tests. The Kolmogorov-Smirnov test for normality showed that all the continuous data except those for percentage (%) distributions were normally distributed. Level of significance was set a-priori at p < 0.05, but type 1 error from multiple comparisons was controlled for by using Bonferroni correction for each subcategory of comparison. In a posthoc exploratory analysis, we compared responses of trainees and consultant psychiatrists. Finally, variables that significantly differed between ‘high’ and ‘low’ antipsychotic polypharmacy prescribers in bivariate analysis were entered into a backward elimination, multivariable logistic regression model to identify independent predictors of ‘high’ versus ‘low’ polypharmacy prescribing patterns.
2. Methods 2.1. Study location and setting This study was conducted between January and September 2013. All public hospitals offering specialist psychiatric services were enumerated and psychiatrists and senior psychiatric trainees were approached to participate in the study. In Nigeria, the majority of psychiatrists work in publically-funded hospitals. Data in this report were collected from consultant psychiatrists and mostly senior psychiatric trainees practicing at 14 hospitals, i.e., 7 standalone hospitals (out of a total of 8 standalone hospitals in Nigeria) and 7 departments of psychiatry in teaching hospitals (out of a total of 18 departments of psychiatry in teaching hospitals in Nigeria). The standalone hospitals account for up to 70% of trainees and psychiatrists. Of the eight standalone hospitals in Nigeria, two were located in the same geographic area, of which one was selected. Of the 18 departments of psychiatry, where more than one centre existed in the same geographic area, only one was selected. In selecting departments, a preference was given to larger departments having a greater patient load, and more consultants and trainees. Each facility offers inpatient and outpatient services, and acute as well as chronic care.
3. Results 3.1. Prescriber demographic characteristics A total of 200 questionnaires were sent out. One hundred and forty two questionnaires were returned. However, 10 questionnaires were incompletely filled out with over 20% of the sections left blank and were thus discarded. Therefore, 132 questionnaires were coded and analysed. Of the 132 participants, thirty four were consultants (25.8%), while the rest were senior residents with at least three years of experience in postgraduate psychiatry practice and training. On average, participants reported that 49.6% of their time was spent on psychopharmacological interventions, with less time being dedicated to psychotherapy (13.2%), research (14.0%), administration (8.3%), or a sub-specialty interest (6.6%) (Table 1).
2.2. Instruments The Prescribers Reasons for Antipsychotic Combination Treatment Questionnaire (PRACT-Q) (Correll et al., 2011; Kishimoto et al., 2013), was utilized in this study. The PRACT-Q assesses the following areas: 135
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Table 1 Characteristics of Prescribers, Antipsychotic Combinations and Antipsychotic Co-treatment History. Characteristic Prescriber demographics Consultant psychiatrist: n, (%) Duration of practice: mean (SD) years Antipsychotic combinations (median %) Any combination SGA+FGA SGA+SGA FGA+FGA Specific combinations: n (%) haloperidol+chlorpromazine trifluoperazine+chlorpromazine risperidone+chlorpromazine Antipsychotic co-treatment history (median %) Patients successfully switched to monotherapy Patients unsuccessfully switched to monotherapy Switch to monotherapy not attempted a
Total (n=132)
≤30% (n=73)
> 30% (n=59)
X2/t/MWUa`
df
p
34 (25.8) 5.20 (4.92)
17 (23.3) 5.23 (5.61)
17 (28.8) 5.17 (3.89)
0.47 0.08
1 131
0.55 0.94
30.00 20.00 0.00 48.00
20.00 20.00 0.00 40.00
60.00 20.00 0.00 60.00
0.00 1684.00 1769.50 1516.00
23 (17.4) 10 (7.6) 5 (3.8)
8 (34.8) 6 (60.0) 2 (40.0)
15 (65.2) 4 (40.0) 3 (60.0)
4.71 0.10 0.49
45.00 15.00 25.00
60.00 12.00 10.00
30.00 20.00 30.00
1118.0 1668.0 1437.50
0.001a 0.03a 0.05a 0.003a 1 1 1
0.03 0.75 0.48 0.001a 0.03a 0.001a
Man-Whitney U.
score=4.3, each), or potential drug-drug interaction, increased nonadherence, lack of evidence base, and higher total dosage of antipsychotic (mean score=3.9, each).
3.2. Prescribing practices Participants reported that on average 36.2 ± 26.3% (mean ± SD) of their patients treated with antipsychotics were prescribed antipsychotic combinations (i.e., antipsychotic polypharmacy). Participants reported that in their patients on antipsychotic polypharmacy, they had never attempted a reduction in number of medications in 26.8 ± 25.9% of cases, had unsuccessfully attempted to convert to monotherapy in 17.4 ± 17.0% of cases, while successful attempts had been made in 45.5 ± 30.4% of cases (Table 1). The most preferred combinations according to class of antipsychotics were first-generation antipsychotics 46.24 ± 32.92%, first- plus second-generation antipsychotics 23.26 ± 22.55%, followed by secondgeneration antipsychotic combinations 7.36 ± 18.45%. As regards specific drug combinations, haloperidol+chlorpromazine (17.4%) combination was most preferred, followed by trifluoperazine+chlorpromazine (7.6%) and risperidone+chlorpromazine (3.8%) (Table 1).
3.4. Post-hoc comparison of psychiatrists and trainees Comparing responses of mostly senior trainees (n=98) and consultant psychiatrists (n=34), results were generally concordant (overall antipsychotic polypharmacy rate: 34.8 ± 26.3% vs. 40.2 ± 26.0%, p=0.30), without significant differences in responses and attitudes related to antipsychotic polypharmacy of (except for cognition as a reason for antipsychotic polypharmacy (p=0.06), all p-values were > 0.10, detailed data not shown). 3.5. Prevalence and correlates of ‘high’ antipsychotic polypharmacy vs. ‘low’ antipsychotic polypharmacy prescribers Compared to ‘low’ antipsychotic polypharmacy prescribers (≤30% antipsychotic polypharmacy), ‘high’ prescribers ( > 30% antipsychotic polypharmacy) reported treating significantly more of their patients with first-generation antipsychotic combination antipsychotic polypharmacy (55.2 ± 26.4% vs. 38.8 ± 33.6%, p=0.003) and to have attempted a switch to monotherapy in significantly less patients (34.2 ± 25.1% vs. 20.5 ± 21.3%, p=0.001) or been successful in doing so (32.1 ± 22.0% vs. 56.0 ± 28.8%, p=0.001) (Table 1). ‘High’ and ‘low’ antipsychotic polypharmacy prescribers were equally moderately concerned about the effects of antipsychotic polypharmacy (3.92 ± 0.88 vs. 4.16 ± 1.13, p=0.17 and also did not differ regarding any reasons not justifying/against antipsychotic polypharmacy (Table 3). However, high antipsychotic polypharmacy prescribers significantly more likely believed that one antipsychotic was insufficient to prevent relapse (p < 0.01), used antipsychotic polypharmacy to speed up treatment effect (p < 0.002), and reduced both the dose of the first antipsychotic (p=0.001) and the number of non-antipsychotic medications (p=0.01) when using antipsychotic polypharmacy (Table 2). Additional reasons that were significantly more likely endorsed by ‘high’ antipsychotic polypharmacy prescribers in univariate analyses included treatment of comorbid conditions and minimization of acute or chronic adverse effects (p=0.02), each, managing residual positive symptoms (p < 0.03) and enhancing efficacy in general (p=0.04), yet these significance levels did not survive correction for multiple comparisons. Finally entering significant variables in the bivariate analyses into a multivariable, backward elimination logistic regression model yielded three independent correlates of ‘high’ vs. ‘low’ antipsychotic polyphar-
3.3. Attitudes towards antipsychotic polypharmacy Participants’ concern about the problems that antipsychotic polypharmacy poses to patients was ‘moderate’ (4.1 ± 1.0). Ratings of reasons supporting antipsychotic polypharmacy use varied between a mean score of 1.7–3.2, ranging from the less important possibility to reduce the number of non-antipsychotic medications (mean score=1.7), one antipsychotic being insufficient to prevent relapse and family choice (mean score=2.0, each =‘a little bit’), to failure of a clozapine trial, intolerance of a clozapine trial, ongoing cross-titration, treatment of comorbid condition, failure of one, two or three sufficient antipsychotic trials, two different routes of administration and enhancement of drug effect (mean scores=2.8–3.2, each =’somewhat’) (Table 2). Of note, in the prescribers’ opinion justification for antipsychotic polypharmacy differed little whether the evidence came from case reports (mean score=2.4), open trials (mean score=2.5), randomized controlled trials (mean score=2.7), or clinical wisdom alone (mean score=2.7). The commonest symptoms practitioners believed that justified antipsychotic polypharmacy (mean score ≥2.8) were aggression and insomnia. The symptoms least endorsed to justify antipsychotic polypharmacy were cognitive symptoms and anxiety (mean score < 2.0) (Table 2). On the other hand, ratings of reasons against antipsychotic polypharmacy use were all at a mean score of ≥3.6 to 4.3 (‘somewhat’ to ‘a lot’), ranging from concerns about cost or increased likelihood for mortality (3.6) to increased risk of acute or chronic side effects (mean 136
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Table 2 Prescriber-Rated Justification for Antipsychotic Polypharmacy. Justification for Antipsychotic Polypharmacy (rating 1–5) Antipsychotic treatment/history Failure of a clozapine trial Intolerance of a clozapine trial Failure of two antipsychotic trials Failure of at least three antipsychotic trials Different route of administration Failure of one antipsychotic trial Recommended by prior healthcare provider One antipsychotic insufficient to prevent relapse Improving outcomes Treatment of a comorbid condition Targeting different symptoms Speed up effect Minimise acute/chronic side effects Reduce dose of first antipsychotic Reduce number of non-antipsychotic medications Level of evidence for Antipsychotic Polypharmacy efficacy Double blind RCT Open label trials Case reports Other Clinical wisdom Different pharmacological mechanism Patients’/family choice Symptoms of mental illness Aggression Insomnia Suicidality Residual negative symptoms Residual positive symptoms Residual agitation Depression Anxiety Cognitive symptoms
Total (n=132)
≤30% (n=73)
> 30% (n=59)
t¶
p
3.24 ± 1.48 3.02 ± 1.47 2.91 ± 1.36 2.89 ± 1.53 2.80 ± 1.41 2.75 ± 1.33 2.20 ± 3.90 1.95 ± 1.25
3.10 ± 1.50 2.97 ± 1.46 2.85 ± 1.42 2.79 ± 1.43 2.62 ± 1.41 2.63 ± 1.36 1.76 ± 0.90 1.68 ± 1.04
3.41 ± 1.45 3.09 ± 1.50 2.98 ± 1.30 3.02 ± 1.64 3.02 ± 1.40 2.89 ± 1.29 2.72 ± 2.68 2.28 ± 1.39
−1.18 −0.44 −0.54 −0.83 −1.60 −1.10 −1.36 −2.76
0.24 0.66 0.59 0.40 0.11 0.27 0.17 0.01
2.95 ± 1.22 2.55 ± 1.25 2.33 ± 1.31 2.21 ± 1.18 2.09 ± 1.06 1.67 ± 0.93
2.71 ± 1.29 2.46 ± 1.33 2.01 ± 1.23 1.99 ± 1.15 1.810.94 1.49 ± 0.86
3.22 ± 1.07 2.67 ± 1.15 2.72 ± 1.31 2.47 ± 1.18 2.44 ± 1.11 1.91 ± 0.97
−2.41 −0.97 −3.11 −2.38 −3.43 −2.55
0.02* 0.33 0.002 0.02* 0.001 0.01
2.72 ± 1.47 2.51 ± 1.29 2.36 ± 1.19
2.38 ± 1.32 2.59 ± 1.48 2.33 ± 1.28
2.60 ± 1.28 2.86 ± 1.46 2.36 ± 1.15
−0.96 −1.01 −0.16
0.31 0.31 0.86
2.65 ± 1.23 2.61 ± 1.22 1.98 ± 1.10
2.66 ± 1.26 2.42 ± 1.23 1.96 ± 1.12
2.65 ± 1.22 2.84 ± 1.18 2.02 ± 1.08
0.04 −1.97 −0.31
0.97 0.05 0.76
2.95 ± 1.24 2.76 ± 1.28 2.58 ± 1.46 2.51 ± 1.24 2.34 ± 1.24 2.31 ± 1.17 2.25 ± 1.24 1.97 ± 1.08 1.96 ± 1.17
2.79 ± 1.21 2.66 ± 1.25 2.47 ± 1.42 2.42 ± 1.31 2.13 ± 1.19 2.18 ± 1.19 2.10 ± 1.24 1.81 ± 1.06 1.93 ± 1.22
3.16 ± 1.27 2.88 ± 1.30 2.73 ± 1.52 2.61 ± 1.15 2.60 ± 1.25 2.46 ± 1.11 2.45 ± 1.23 2.16 ± 1.07 2.00 ± 1.09
−1.68 −0.97 −1.03 −0.86 −2.20 −1.36 −1.61 −1.81 −0.35
0.09 0.33 0.31 0.39 0.03* 0.18 0.11 0.07 0.73
Anchors for the ratings of the degree by which prescribers felt antipsychotic polypharmacy was or was not justified based on provided characteristics: 5-point Likert scale: 1= not at all (=0%) 2=a little bit (=25%), 3=somewhat (=50%), 4=a lot (=75%), 5=a whole lot (100% justified) * Not significant after Bonferroni correction; ¶ df=131.
4. Discussion
macy prescribing explaining 24.9% of the variance: respondents who had ‘successfully switched patients to monotherapy’ were significantly less likely to be among the ‘high’ antipsychotic polypharmacy prescribers (OR=0.02, 95% CI: 0.002–0.08, p < 0.0001), whereas those preferring first-generation antipsychotic +first generation antipsychotic combinations (OR=13.86, 95%CI: 3.29–68.50, p < 0.01) and those aiming for a reduction of non-antipsychotic medications (OR=5.46, 95%CI:1.48–21.98, p < 0.013) were more likely among the ‘high’ antipsychotic polypharmacy prescribers (overall model: r2=0.249, p < 0.0001).
This study found that consultant psychiatrists and senior trainees surveyed in Nigeria reported prescribing antipsychotic polypharmacy in over a third of their patients. There were no significant differences based on level of training, likely due to the fact that trainees were generally senior residents and that the composition of the case load in Nigeria does not differ systematically between trainees and consultant psychiatrists. ‘High’ vs. ‘low’ antipsychotic polypharmacy use did not differ significantly based on prescriber characteristics. Similarly, there were no differences regarding reasons against antipsychotic polypharmacy, which were generally rated with higher ratings compared with justification for antipsychotic polypharmacy. Conversely, ‘high’ anti-
Table 3 Prescriber-Rated Lack of Justification for Antipsychotic Polypharmacy. Lack of Justification for Antipsychotic Polypharmacy
Total (n=132)
≤30% (n=73)
> 30% (n=59)
ta
p
Increased risk of chronic side effects Increased risk of acute side effects Potential for drug-drug interaction Increased risk of non-adherence Lack of evidence base High total dose of AP Difficulty determining cause and effect Increased mortality Potential for increased cost
4.32 ± 1.01 4.31 ± 0.98 3.88 ± 1.10 3.87 ± 1.04 3.87 ± 1.18 3.86 ± 1.19 3.82 ± 3.71 3.60 ± 1.37 3.58 ± 1.14
4.34 ± 0.98 4.26 ± 1.05 3.79 ± 1.19 3.82 ± 1.09 3.94 ± 1.16 3.79 ± 1.21 4.11 ± 1.87 3.56 ± 1.38 3.60 ± 1.10
4.29 ± 1.06 4.36 ± 0.89 3.98 ± 0.97 3.93 ± 0.98 3.78 ± 1.20 3.95 ± 1.16 3.45 ± 1.11 3.64 ± 1.36 3.56 ± 1.19
0.28 −0.59 −0.98 −0.61 0.79 −0.74 1.01 −0.36 0.22
0.78 0.56 0.33 0.54 0.43 0.46 0.31 0.72 0.82
Anchors for ratings of how much prescribers globally feel that antipsychotic polypharmacy is problematic: 7-point Likert scale: 1= not at all, 2=minimal, 3=mild, 4=moderate, 5=marked, 6=severe, 7=extreme a df=131.
137
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2011). Notably, Nigerian prescribers ranked evidence supporting antipsychotic polypharmacy relatively similar independent of the strength of the evidence, making little differentiation between evidence based on case reports, open trials or randomized controlled trials. They ranked clinical wisdom as high as randomized clinical trials. This was not the case in the US and Japanese surveys where clinical wisdom ranked lowest and randomized clinical trials ranked highest, suggesting a potential for educational needs for Nigerian psychiatrists and trainees. In the current survey, prescribers reported that 45% of their patients on antipsychotic polypharmacy could be converted successfully to monotherapy. This was a higher reported conversion rate when compared with the US and Japanese surveys (28% each) (Correll et al., 2011; Kishimoto et al., 2013). This difference could possibly be related to the frequent use of antipsychotic polypharmacy in acute settings to speed up treatment response in Nigeria, rather than its use as an augmentation strategy in refractory patients. In Nigeria, ‘high’ antipsychotic polypharmacy prescribers were less likely to manage patients who they had successfully switched to monotherapy and they were treating more patients in whom they had never attempted a switch to antipsychotic monotherapy. This finding underscores the impact that attitudes may have on actual prescribing practices. However, the opposite could also be true, in that less success prevents clinicians from trying a switch to antipsychotic monotherapy. Lack of a successful switch was reported in 17% of patients in Nigeria compared to 24% in the US and 37% in the Japanese survey (Correll et al., 2011; Kishimoto et al., 2013). Nevertheless, it is surprising that still 27%, 35% and 41% of the patients on antipsychotic polypharmacy in the Nigerian, Japanese and US surveys were reported as not having been tried to revert from antipsychotic polypharmacy to antipsychotic monotherapy, suggesting either some therapeutic inertia or fear of deterioration in patients who are seen as stable or, at least, somewhat improved on an antipsychotic polypharmacy regimen. In fact, the literature on converting patients on antipsychotic polypharmacy to monotherapy suggests that between half and twothirds of patients on antipsychotic polypharmacy can safely and effectively be converted to antipsychotic monotherapy (Tani et al., 2013; Essock et al., 2011; Suzuki et al., 2005, 2004). However, these figures also mean that clinicians attempting such a switch may see worsening in a subgroup of patients, deterring them from attempting such a switch in the future. Clearly, studies are needed that identify patient and treatment characteristics associated with a successful conversion from antipsychotic polypharmacy to antipsychotic monotherapy to help guide clinicians. Our findings should be viewed with the following limitations in mind. First, the sample size was moderate. Second, although recruitment was spread across the country, the non-response rate was high, which may result in a selection bias. Third, the antipsychotic polypharmacy rates reported and views expressed by clinicians may not fully reflect actual practice, as they may provide responses they deemed appropriate as regards published evidence and treatment guidelines. However, we were unable to obtain and link actual prescription data to individual survey respondents. Fourth, there was a skew towards more senior trainees than consultants in the sample, and trainees may be reflecting the views of their trainers or consultants or report practices that have been handed down to them. Finally, information on the diagnoses, target symptoms and severity of illness/impairment of the patients prescribed antipsychotic polypharmacy by the surveyed clinicians was not available nor were data on efficacy and tolerability of antipsychotic polypharmacy or on the views of patients and families assessed in this survey study. This missing data may explain why in our multivariate model, only 25% of the variance between high and low antipsychotic polypharmacy prescribers could be explained. Thus, future studies should aim to both record actual antipsychotic polypharmacy prescription rates of survey respondents and collect information on additional patient and prescriber characteristics that may
psychotic polypharmacy prescribing was significantly associated with the use of first-generation antipsychotic combinations, a lower frequency of a successful conversion of patients from antipsychotic polypharmacy to monotherapy and lack of any previous attempts of switching to antipsychotic monotherapy. Regarding attitudes, ‘high’ antipsychotic polypharmacy prescribers were more likely to endorse the opinion that one antipsychotic was insufficient to prevent a relapse, and believed that antipsychotic polypharmacy will speed up treatment effect. ‘High’ antipsychotic polypharmacy prescription was also often motivated by a desire to reduce the dose of the first antipsychotic as well as reduce the number of non-antipsychotic medications. The reported prevalence of antipsychotic polypharmacy in this study is within the range of rates (7% and 55.4%) obtained from patient audits from previous studies in Nigeria (Adelufosi et al., 2013; Adesola et al., 2013). Compared to similar reports assessing psychiatrists prescription practices for antipsychotic polypharmacy, the frequency was higher than that reported in the United States (17.0%) (Correll et al., 2011) but lower when compared to the frequency from Japan (47.7%) (Kishimoto et al., 2013). The preference for combining first-generation antipsychotics was also reported in one audit in Nigeria (Adelufosi et al., 2013). Conversely, in the US survey, 1.1% of patients were reported to receive two first-generation antipsychotics (Correll et al., 2011), whereas the rate was 17.2% in the Japanese prescriber survey (Kishimoto et al., 2013). The first-generation antipsychotic cotreatment preference may well be reflective of the types of medications available for use by psychiatrists in Nigeria. Since data on extrapyramidal side effects, anticholinergic use, prolactin levels and sexual dysfunction were unavailable, it is unclear to what degree this practice in Nigeria is associated with these adverse effects. Although second generation antipsychotics are now more readily available in Nigeria and other parts of Africa, they are usually more expensive and cannot be afforded by the majority of patients who pay for their care ‘out-ofpocket’. Unlike in other settings in Europe, North America and some countries in Asia where health insurance schemes provide coverage for large sections of the mentally ill, a vast majority of patients rely on their relatives to pay for care, particularly when they are unable to work due to the severity of their mental illness. Future studies in this setting are needed to explore the impact that limited access to an array of medications have on the prescribing habits of psychiatrists in the Nigeria. In the US, Japanese and Nigerian surveys ongoing cross-titration and failure or intolerance to clozapine were consistently among the highest rated reasons justifying antipsychotic polypharmacy. However, in the Nigerian survey, a different route of administration and different pharmacological mechanisms ranked not as high as in the Japanese and the US survey, which may also have to do with a more restricted psychiatric medication armamentarium. Conversely, reducing the number of non-antipsychotic medications was seen as a particular advantage by ‘high’ antipsychotic polypharmacy users in Nigeria, whereas this focus did not differentiate ‘high’ and low’ antipsychotic polypharmacy users in the other two similar surveys (Correll et al., 2011; Kishimoto et al., 2013). Whether clinicians in Nigeria try reserving other, potentially more expensive medications by combining two first-generation antipsychotics or whether they are attempting to delay use of benzodiazepines with abuse potential, by adding a low potency to a high potency first-generation antipsychotic, is suggested by the fact that chlorpromazine was one of the first-generation antipsychotics in the three most utilized combinations. This potential reason for this finding is unclear and should be examined further. Interestingly, ‘high’ antipsychotic polypharmacy users also reported that one goal of antipsychotic polypharmacy was to speed up the effect of medications. In Nigeria, as in other low and middle income countries, individuals with psychotic disorders present late to services and often with severe symptoms. Due to constraints for bed spaces and treatment costs, psychiatrists may therefore prefer combining antipsychotics hoping to hasten treatment response and discharge (James, 138
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monotherapy. Am. J. Psych. 168 (7), 702–708. Falkai, P., Wobrock, D.T., Lieberman, J., Glenthoj, B., Gattaz, W.F., Möller, H.J., 2009. World federation of Societies of biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, Part 1: acute treatment of schizophrenia. World J. Biol. Psychiatry. Fleischhacker, W.W., Uchida, H., 2012. Critical review of antipsychotic polypharmacy in the treatment of schizophrenia. Int. J. Neuropsychopharmacol. 17 (07). Gallego, J.A., Bonetti, J., Zhang, J., Kane, J.M., Correll, C.U., 2012a. Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009. Schiz. Res. 138 (1), 18–28. Gallego, J.A., Nielsen, J., De Hert, M., Kane, J.M., Correll, C.U., 2012b. Safety and tolerability of antipsychotic polypharmacy. Expert Opin. Drug Saf. 11 (4), 527–542. Iasevoli, F., Buonaguro, E.F., Marconi, M., Di Giovambattista, E., Rapagnani, M.P., De Berardis, D., Valchera, A., 2014. Efficacy and clinical determinants of antipsychotic polypharmacy in psychotic patients experiencing an acute relapse and admitted to hospital stay: results from a cross-sectional and a subsequent longitudinal pilot study. ISRN Pharm. 762127. Ito, H., Koyama, A., Higuchi, T., 2005. Polypharmacy and excessive dosing: psychiatrists' perceptions of antipsychotic drug prescription. Br. J. Psych. 187 (3), 243–247. James, B.O., 2011. Rapid tranquillization agents for severe behavioural disturbance: a survey of African psychiatrists' prescription patterns. Trop. Dr. 41 (1), 49–50. Kishimoto, T., Watanabe, K., Uchida, H., Mimura, M., Kane, J.M., Correll, C.U., 2013. Antipsychotic polypharmacy: a Japanese survey of prescribers' attitudes and rationales. Psych. Res. 209 (3). Koen, L., Magni, P., Niehaus, D.J., le Roux, A., 2008. Antipsychotic prescription patterns in Xhosa patients with schizophrenia or schizoaffective disorder. Afr. J. Psych. 11 (4), 287–290. Li, Q., Xiang, Y.-T., Su, Y.-A., Shu, L., Yu, X., Chiu, H.F., Si, T.M., 2015. Antipsychotic polypharmacy in schizophrenia patients in China and its association with treatment satisfaction and quality of life: findings of the third national survey on use of psychotropic medications in China. Aust. N. Z. J. Psych.. Lochmann van Bennekom, M.W.H., Gijsman, H.J., Zitman, F.G., 2013. Antipsychotic polypharmacy in psychotic disorders: a critical review of neurobiology, efficacy, tolerability and cost effectiveness. J. Psychopharmacol. 27 (4), 327–336. Sernyak, M.J., Rosenheck, R., 2004. Clinicians' reasons for antipsychotic coprescribing. J. Clin. Psych. 65 (12), 1597–1600. Suzuki, T., Uchida, H., Takeuchi, H., Nomura, K., Tanabe, A., Watanabe, K., Yagi, G., H, K., 2005. Simplifying psychotropic medication regimen into a single night dosage and reducing the dose for patients with chronic schizophrenia. Psychopharmacol. (Berl.). 181 (3), 566–575. Suzuki, T., Uchida, H., Watanabe, K., Yagi, G., Kashima, H., 2004. A clinical case series of switching from antipsychotic polypharmacy to monotherapy with a secondgeneration agent on patients with chronic schizophrenia. Prog. NeuroPsychopharmacol. Biol. Psych. 28 (2), 361–369. Tani, H., Uchida, H., Suzuki, T., Fujii, Y., Mimura, M., 2013. Interventions to reduce antipsychotic polypharmacy: a systematic review. Schiz. Res. 143 (1), 215–220. Taylor, D.M., Smith, L., Gee, S.H., Nielsen, J., 2012. Augmentation of clozapine with a second antipsychotic - a meta-analysis. Acta Psych. Scand. 125 (1), 15–24. Tsutsumi, C., Uchida, H., Suzuki, T., Watanabe, K., Takeuchi, H., Nakajima, S., Kapur, S., 2011. The evolution of antipsychotic switch and polypharmacy in natural practice–a longitudinal perspective. Schizo. Res. 130 (1–3), 40–46.
explain antipsychotic polypharmacy prescription behaviour. In summary, our findings identify relevant prescriber characteristics that differentiate ‘high’ from ‘low’ antipsychotic polypharmacy users. These results can inform educational campaigns and performance improvement projects, namely the guided attempt at converting patients successfully from antipsychotic polypharmacy to antipsychotic monotherapy. Going forward, identifying interventions to reduce antipsychotic polypharmacy prescribing among psychiatrists are desirable. As earlier reported, education is considered a passive and relatively ineffective intervention, rather, active interventions have shown some promise (Fleischhacker and Uchida, 2012). Actual prescription monitoring and feedback significantly reduced antipsychotic polypharmacy prescribing. However, the feasibility of such interventions in a low income setting is debatable because of poor and ineffective health system monitoring and the absence of locally relevant guidelines. Future studies should explore what strategies may be effective in reducing high antipsychotic polypharmacy prescribing, which should only be an option of last resort, and in which subgroups of patients antipsychotic polypharmacy may be useful or needed (Essock et al., 2011; Tani et al., 2013). References Adelufosi, A., Abayomi, O., Tolulope, O., 2013. Antipsychotic polypharmacy and excessive dosing in Nigerian patients with schizophrenia: prevalence, correlates and relationship with quality of life. Biol. Psych. 73 (9), 213S. Adesola, A., Anozie, I., Erohubie, P., James, B., 2013. Prevalence and correlates of ‘high dose’ antipsychotic prescribing: findings from a hospital audit. Ann. Med. Health Sci. Res. 3 (1), 62–66. Barbui, C., Signoretti, A., Mulè, S., Boso, M., Cipriani, A., 2009. Does the addition of a second antipsychotic drug improve clozapine treatment? Schiz. Bull 35 (2), 458–468. Chang, J., Kim, B., 2014. A survey study of the satisfaction and attitude of the Korean psychiatrists toward antipsychotic polypharmacy. Ann. Clin. Psych. 26 (1), 64–69. Correll, C.U., Gallego, J.A., 2012. Antipsychotic polypharmacy: a comprehensive evaluation of relevant correlates of a long-standing clinical practice. Psych. Clin. N. Am. 35 (3), 661–681. Correll, C.U., Rummel-Kluge, C., Corves, C., Kane, J.M., Leucht, S., 2009. Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schiz. Bull. 35 (2), 443–457. Correll, C.U., Shaikh, L., Gallego, J.A., Nachbar, J., Olshanskiy, V., Kishimoto, T., Kane, J.M., 2011. Antipsychotic polypharmacy: a survey study of prescriber attitudes, knowledge and behavior. Schiz. Res. 131 (1–3), 58–62. Essock, S.M., Schooler, N.R., Stroup, T.S., McEvoy, J.P., Rojas, I., Jackson, C., Covell, N.H., 2011. Effectiveness of switching from antipsychotic polypharmacy to
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Attitudes towards and rationale for antipsychotic polypharmacy among psychiatrists in Nigeria: Characteristics associated with high reported antipsychotic polypharmacy
MARK
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B.O. Jamesa, , J.O. Omoaregbaa, S.O. Rajia, O.E. Imishueb, K.M. Okonodac,i, Y.I. Nyamalid, P.A. Famuyiwae, C.U. Correllf,g,h a
Department of Clinical Services, Federal Neuro-Psychiatric Hospital, Benin-City, Nigeria Department of Clinical Services, Neuro-Psychiatric Hospital, Aro, Abeokuta, Nigeria Department of Psychiatry, University of Jos, Jos, Plateau State, Nigeria d Department of Clinical Services, Federal Neuro-Psychiatric Hospital, Yaba, Lagos, Nigeria e Department of Clinical Services, Federal Neuro-Psychiatric Hospital, Calabar, Cross River, Nigeria f The Zucker Hillside Hospital, Psychiatry Research, Northwell Health System, Glen Oaks, NY, USA g Hofstra Northwell School of Medicine, Hempstead, NY, USA h The Feinstein Institute for Medical Research, Manhasset, NY, USA i Jos University Teaching Hospital, Jos, Plateau State, Nigeria b c
A R T I C L E I N F O
A BS T RAC T
Keywords: Antipsychotic polypharmacy Rationale Reasons Survey Psychiatrists Nigeria
Antipsychotic polypharmacy (APP) is commonplace despite lacking evidence of its effectiveness. We aimed to identify psychiatrists’ rationale for and attitudes towards APP and to determine if attitudes influence antipsychotic polypharmacy prescription rates in a survey of a nationally representative sample of Nigerian psychiatrists (of which a majority were senior trainees: 74.2%). Prescriber characteristics, practices and attitudes were compared in ‘high’ ( > 30%) vs. ‘low’ (≤30%) antipsychotic polypharmacy prescribers and results were adjusted for multiple comparisons. Altogether, prescribers reported utilizing antipsychotic polypharmacy in 36.2% of their patients. Compared to ‘low’ antipsychotic polypharmacy prescribers, ‘high’ prescribers were significantly more likely using first-generation antipsychotics (FGA) combination, to have attempted a switch to monotherapy in less patients, or been successful in doing so. ‘High’ and ‘low’ antipsychotic polypharmacy prescribers were equally moderately concerned about the effects of antipsychotic polypharmacy and also did not differ regarding reasons not justifying antipsychotic polypharmacy. In a multivariable, backward elimination logistic regression model, ‘low’ antipsychotic polypharmacy was associated with having successfully switched patients to monotherapy, whereas the ‘high’ antipsychotic polypharmacy was associated with preferring FGA +FGA combinations and aiming for a reduction of non-antipsychotic medications. Antipsychotic polypharmacy is common among psychiatrists in Nigeria, with ‘high’ and ‘low’ antipsychotic polypharmacy prescribers sharing similar concerns/attitudes, but differing regarding their primary aim for antipsychotic polypharmacy and in their specific antipsychotic polypharmacy use characteristics.
1. Introduction Antipsychotic polypharmacy is common in psychiatric practice (Correll et al., 2011; Kishimoto et al., 2013). Rates of antipsychotic polypharmacy vary around the world (Gallego et al., 2012a; Li et al., 2015), and antipsychotic polypharmacy is associated with higher antipsychotic doses and more frequent adverse effects related to dopamine blockade as well as greater anticholinergic medication use (Adesola et al., 2013; Correll and Gallego, 2012; Gallego et al., 2012b;
⁎
Koen et al., 2008). Due to lacking evidence for the efficacy and safety of antipsychotic polypharmacy (Barbui et al., 2009; Correll et al., 2009; Gallego et al., 2012b; Lochmann van Bennekom et al., 2013; Taylor et al., 2012)., clinical guidelines recommend antipsychotic monotherapy, especially in the acute phases of schizophrenia-related illnesses, recommending also clozapine and not antipsychotic polypharmacy for treatment resistant patients (Falkai et al., 2009). Despite these guidelines and insufficient database supporting its use, antipsychotic polypharmacy has remained common among clients receiving antipsychotic
Corresponding author. E-mail address: [email protected] (B.O. James).
http://dx.doi.org/10.1016/j.psychres.2016.12.032 Received 29 February 2016; Received in revised form 29 October 2016; Accepted 24 December 2016 Available online 27 December 2016 0165-1781/ © 2016 Elsevier Ireland Ltd. All rights reserved.
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medications (Chang and Kim, 2014; Gallego et al., 2012a). Given the absence of convincing data supporting its use antipsychotic polypharmacy, is reflective of the practice-based prescribing preferences of psychiatrists who may have a clinical rationale for instituting and maintaining antipsychotic polypharmacy for certain patient subgroups and under specific conditions. Individualized clinical decision making as an underlying reason for antipsychotic polypharmacy is also indicated by wide practice and regional variations in antipsychotic polypharmacy frequency in surveys conducted at the same time and in the same country and health care setting (Correll and Gallego, 2012; Correll et al., 2011). A disconnect between evidence and guidelines on the one hand and clinical practice on the other makes it pertinent to understand reasons for attitudes towards and characteristics of antipsychotic polypharmacy from the practitioners’ perspective. The complexity of this clinical practice example is exemplified by the fact that some studies have indicated that, at least, in some clinical situations antipsychotic polypharmacy may be associated with better treatment response (Correll et al., 2009) or quality of life (Li et al., 2014). Furthermore, antipsychotic polypharmacy may be attempted after observed “inefficacy” of just one antipsychotic trials and despite low dose monotherapy treatment in almost half of those patients (Tsutsumi et al., 2011). On the other hand, antipsychotic polypharmacy has also been associated with a greater number of some side effects (Gallego et al., 2012b; Li et al., 2015), yet other side effects may be reduced, especially when adding a partial D2 agonist to a full D2 antagonist (Gallego et al., 2012b). Reports on practitioners’ perspectives on antipsychotic polypharmacy to better understand antipsychotic polypharmacy decision making and practice have been few and have largely been undertaken in North America, Europe and Asia (Correll et al., 2011; Kishimoto et al., 2013; Ito et al., 2005; Sernyak and Rosenheck, 2004; IasevoLi et al., 2014). This study, therefore, sought to ascertain the reported prevalence of antipsychotic polypharmacy among psychiatrists in Nigeria as well as to identify reasons for and correlates of prescribing patterns of antipsychotic polypharmacy using a self-administered, semi-structured questionnaire that has been used previously for the same purpose (Correll et al., 2011; Kishimoto et al., 2013).
self-reported, estimated percentage of patients on antipsychotic polypharmacy; preferred antipsychotic combination(s); estimated percentage of patients in whom conversion to antipsychotic monotherapy was attempted and if it was successful or unsuccessful; how much prescribers globally feel that antipsychotic polypharmacy is problematic (using a 7-point Likert scale: 1=not at all, 2=minimal, 3=mild, 4=moderate, 5=marked, 6=severe, 7=extreme); as well as attitudes regarding specific reasons for and reasons against antipsychotic polypharmacy (using a 5-point Likert scale assessing the degree by which prescribers felt antipsychotic polypharmacy was or was not justified based on provided characteristics: 1= not at all (=0%) 2=a little bit (=25%), 3=somewhat (=50%), 4=a lot (=75%), 5=a whole lot (100% justified) (Kishimoto et al., 2013).
2.3. Ethical considerations All participating prescribers were assured of complete confidentiality and anonymity. No identifying information was obtained, and participants were free to decline to participate in or opt out of this research study. Each questionnaire contained an information sheet, and participants were deemed to have provided informed consent when they read and proceeded to complete the questionnaire.
2.4. Data analysis Data were analysed using the Statistical Package for Social Sciences (SPSS) Software version 20 (SPSS Inc.). Data were summarized using descriptive statistics. Prescriber characteristics, practices and attitudes were compared in ‘high’ ( > 30%) vs. ‘low’ (≤30%) antipsychotic polypharmacy prescribers, using the median split of 30% as done in the previous two studies using the PRACT-Q (Correll et al., 2011; Kishimoto et al., 2013). Bivariate categorical comparisons were performed using the chi-squared test while for continuous data, normally distributed data were compared using the Students’ t-test, and nonnormally distributed data compared using Mann-Whitney U tests. The Kolmogorov-Smirnov test for normality showed that all the continuous data except those for percentage (%) distributions were normally distributed. Level of significance was set a-priori at p < 0.05, but type 1 error from multiple comparisons was controlled for by using Bonferroni correction for each subcategory of comparison. In a posthoc exploratory analysis, we compared responses of trainees and consultant psychiatrists. Finally, variables that significantly differed between ‘high’ and ‘low’ antipsychotic polypharmacy prescribers in bivariate analysis were entered into a backward elimination, multivariable logistic regression model to identify independent predictors of ‘high’ versus ‘low’ polypharmacy prescribing patterns.
2. Methods 2.1. Study location and setting This study was conducted between January and September 2013. All public hospitals offering specialist psychiatric services were enumerated and psychiatrists and senior psychiatric trainees were approached to participate in the study. In Nigeria, the majority of psychiatrists work in publically-funded hospitals. Data in this report were collected from consultant psychiatrists and mostly senior psychiatric trainees practicing at 14 hospitals, i.e., 7 standalone hospitals (out of a total of 8 standalone hospitals in Nigeria) and 7 departments of psychiatry in teaching hospitals (out of a total of 18 departments of psychiatry in teaching hospitals in Nigeria). The standalone hospitals account for up to 70% of trainees and psychiatrists. Of the eight standalone hospitals in Nigeria, two were located in the same geographic area, of which one was selected. Of the 18 departments of psychiatry, where more than one centre existed in the same geographic area, only one was selected. In selecting departments, a preference was given to larger departments having a greater patient load, and more consultants and trainees. Each facility offers inpatient and outpatient services, and acute as well as chronic care.
3. Results 3.1. Prescriber demographic characteristics A total of 200 questionnaires were sent out. One hundred and forty two questionnaires were returned. However, 10 questionnaires were incompletely filled out with over 20% of the sections left blank and were thus discarded. Therefore, 132 questionnaires were coded and analysed. Of the 132 participants, thirty four were consultants (25.8%), while the rest were senior residents with at least three years of experience in postgraduate psychiatry practice and training. On average, participants reported that 49.6% of their time was spent on psychopharmacological interventions, with less time being dedicated to psychotherapy (13.2%), research (14.0%), administration (8.3%), or a sub-specialty interest (6.6%) (Table 1).
2.2. Instruments The Prescribers Reasons for Antipsychotic Combination Treatment Questionnaire (PRACT-Q) (Correll et al., 2011; Kishimoto et al., 2013), was utilized in this study. The PRACT-Q assesses the following areas: 135
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Table 1 Characteristics of Prescribers, Antipsychotic Combinations and Antipsychotic Co-treatment History. Characteristic Prescriber demographics Consultant psychiatrist: n, (%) Duration of practice: mean (SD) years Antipsychotic combinations (median %) Any combination SGA+FGA SGA+SGA FGA+FGA Specific combinations: n (%) haloperidol+chlorpromazine trifluoperazine+chlorpromazine risperidone+chlorpromazine Antipsychotic co-treatment history (median %) Patients successfully switched to monotherapy Patients unsuccessfully switched to monotherapy Switch to monotherapy not attempted a
Total (n=132)
≤30% (n=73)
> 30% (n=59)
X2/t/MWUa`
df
p
34 (25.8) 5.20 (4.92)
17 (23.3) 5.23 (5.61)
17 (28.8) 5.17 (3.89)
0.47 0.08
1 131
0.55 0.94
30.00 20.00 0.00 48.00
20.00 20.00 0.00 40.00
60.00 20.00 0.00 60.00
0.00 1684.00 1769.50 1516.00
23 (17.4) 10 (7.6) 5 (3.8)
8 (34.8) 6 (60.0) 2 (40.0)
15 (65.2) 4 (40.0) 3 (60.0)
4.71 0.10 0.49
45.00 15.00 25.00
60.00 12.00 10.00
30.00 20.00 30.00
1118.0 1668.0 1437.50
0.001a 0.03a 0.05a 0.003a 1 1 1
0.03 0.75 0.48 0.001a 0.03a 0.001a
Man-Whitney U.
score=4.3, each), or potential drug-drug interaction, increased nonadherence, lack of evidence base, and higher total dosage of antipsychotic (mean score=3.9, each).
3.2. Prescribing practices Participants reported that on average 36.2 ± 26.3% (mean ± SD) of their patients treated with antipsychotics were prescribed antipsychotic combinations (i.e., antipsychotic polypharmacy). Participants reported that in their patients on antipsychotic polypharmacy, they had never attempted a reduction in number of medications in 26.8 ± 25.9% of cases, had unsuccessfully attempted to convert to monotherapy in 17.4 ± 17.0% of cases, while successful attempts had been made in 45.5 ± 30.4% of cases (Table 1). The most preferred combinations according to class of antipsychotics were first-generation antipsychotics 46.24 ± 32.92%, first- plus second-generation antipsychotics 23.26 ± 22.55%, followed by secondgeneration antipsychotic combinations 7.36 ± 18.45%. As regards specific drug combinations, haloperidol+chlorpromazine (17.4%) combination was most preferred, followed by trifluoperazine+chlorpromazine (7.6%) and risperidone+chlorpromazine (3.8%) (Table 1).
3.4. Post-hoc comparison of psychiatrists and trainees Comparing responses of mostly senior trainees (n=98) and consultant psychiatrists (n=34), results were generally concordant (overall antipsychotic polypharmacy rate: 34.8 ± 26.3% vs. 40.2 ± 26.0%, p=0.30), without significant differences in responses and attitudes related to antipsychotic polypharmacy of (except for cognition as a reason for antipsychotic polypharmacy (p=0.06), all p-values were > 0.10, detailed data not shown). 3.5. Prevalence and correlates of ‘high’ antipsychotic polypharmacy vs. ‘low’ antipsychotic polypharmacy prescribers Compared to ‘low’ antipsychotic polypharmacy prescribers (≤30% antipsychotic polypharmacy), ‘high’ prescribers ( > 30% antipsychotic polypharmacy) reported treating significantly more of their patients with first-generation antipsychotic combination antipsychotic polypharmacy (55.2 ± 26.4% vs. 38.8 ± 33.6%, p=0.003) and to have attempted a switch to monotherapy in significantly less patients (34.2 ± 25.1% vs. 20.5 ± 21.3%, p=0.001) or been successful in doing so (32.1 ± 22.0% vs. 56.0 ± 28.8%, p=0.001) (Table 1). ‘High’ and ‘low’ antipsychotic polypharmacy prescribers were equally moderately concerned about the effects of antipsychotic polypharmacy (3.92 ± 0.88 vs. 4.16 ± 1.13, p=0.17 and also did not differ regarding any reasons not justifying/against antipsychotic polypharmacy (Table 3). However, high antipsychotic polypharmacy prescribers significantly more likely believed that one antipsychotic was insufficient to prevent relapse (p < 0.01), used antipsychotic polypharmacy to speed up treatment effect (p < 0.002), and reduced both the dose of the first antipsychotic (p=0.001) and the number of non-antipsychotic medications (p=0.01) when using antipsychotic polypharmacy (Table 2). Additional reasons that were significantly more likely endorsed by ‘high’ antipsychotic polypharmacy prescribers in univariate analyses included treatment of comorbid conditions and minimization of acute or chronic adverse effects (p=0.02), each, managing residual positive symptoms (p < 0.03) and enhancing efficacy in general (p=0.04), yet these significance levels did not survive correction for multiple comparisons. Finally entering significant variables in the bivariate analyses into a multivariable, backward elimination logistic regression model yielded three independent correlates of ‘high’ vs. ‘low’ antipsychotic polyphar-
3.3. Attitudes towards antipsychotic polypharmacy Participants’ concern about the problems that antipsychotic polypharmacy poses to patients was ‘moderate’ (4.1 ± 1.0). Ratings of reasons supporting antipsychotic polypharmacy use varied between a mean score of 1.7–3.2, ranging from the less important possibility to reduce the number of non-antipsychotic medications (mean score=1.7), one antipsychotic being insufficient to prevent relapse and family choice (mean score=2.0, each =‘a little bit’), to failure of a clozapine trial, intolerance of a clozapine trial, ongoing cross-titration, treatment of comorbid condition, failure of one, two or three sufficient antipsychotic trials, two different routes of administration and enhancement of drug effect (mean scores=2.8–3.2, each =’somewhat’) (Table 2). Of note, in the prescribers’ opinion justification for antipsychotic polypharmacy differed little whether the evidence came from case reports (mean score=2.4), open trials (mean score=2.5), randomized controlled trials (mean score=2.7), or clinical wisdom alone (mean score=2.7). The commonest symptoms practitioners believed that justified antipsychotic polypharmacy (mean score ≥2.8) were aggression and insomnia. The symptoms least endorsed to justify antipsychotic polypharmacy were cognitive symptoms and anxiety (mean score < 2.0) (Table 2). On the other hand, ratings of reasons against antipsychotic polypharmacy use were all at a mean score of ≥3.6 to 4.3 (‘somewhat’ to ‘a lot’), ranging from concerns about cost or increased likelihood for mortality (3.6) to increased risk of acute or chronic side effects (mean 136
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Table 2 Prescriber-Rated Justification for Antipsychotic Polypharmacy. Justification for Antipsychotic Polypharmacy (rating 1–5) Antipsychotic treatment/history Failure of a clozapine trial Intolerance of a clozapine trial Failure of two antipsychotic trials Failure of at least three antipsychotic trials Different route of administration Failure of one antipsychotic trial Recommended by prior healthcare provider One antipsychotic insufficient to prevent relapse Improving outcomes Treatment of a comorbid condition Targeting different symptoms Speed up effect Minimise acute/chronic side effects Reduce dose of first antipsychotic Reduce number of non-antipsychotic medications Level of evidence for Antipsychotic Polypharmacy efficacy Double blind RCT Open label trials Case reports Other Clinical wisdom Different pharmacological mechanism Patients’/family choice Symptoms of mental illness Aggression Insomnia Suicidality Residual negative symptoms Residual positive symptoms Residual agitation Depression Anxiety Cognitive symptoms
Total (n=132)
≤30% (n=73)
> 30% (n=59)
t¶
p
3.24 ± 1.48 3.02 ± 1.47 2.91 ± 1.36 2.89 ± 1.53 2.80 ± 1.41 2.75 ± 1.33 2.20 ± 3.90 1.95 ± 1.25
3.10 ± 1.50 2.97 ± 1.46 2.85 ± 1.42 2.79 ± 1.43 2.62 ± 1.41 2.63 ± 1.36 1.76 ± 0.90 1.68 ± 1.04
3.41 ± 1.45 3.09 ± 1.50 2.98 ± 1.30 3.02 ± 1.64 3.02 ± 1.40 2.89 ± 1.29 2.72 ± 2.68 2.28 ± 1.39
−1.18 −0.44 −0.54 −0.83 −1.60 −1.10 −1.36 −2.76
0.24 0.66 0.59 0.40 0.11 0.27 0.17 0.01
2.95 ± 1.22 2.55 ± 1.25 2.33 ± 1.31 2.21 ± 1.18 2.09 ± 1.06 1.67 ± 0.93
2.71 ± 1.29 2.46 ± 1.33 2.01 ± 1.23 1.99 ± 1.15 1.810.94 1.49 ± 0.86
3.22 ± 1.07 2.67 ± 1.15 2.72 ± 1.31 2.47 ± 1.18 2.44 ± 1.11 1.91 ± 0.97
−2.41 −0.97 −3.11 −2.38 −3.43 −2.55
0.02* 0.33 0.002 0.02* 0.001 0.01
2.72 ± 1.47 2.51 ± 1.29 2.36 ± 1.19
2.38 ± 1.32 2.59 ± 1.48 2.33 ± 1.28
2.60 ± 1.28 2.86 ± 1.46 2.36 ± 1.15
−0.96 −1.01 −0.16
0.31 0.31 0.86
2.65 ± 1.23 2.61 ± 1.22 1.98 ± 1.10
2.66 ± 1.26 2.42 ± 1.23 1.96 ± 1.12
2.65 ± 1.22 2.84 ± 1.18 2.02 ± 1.08
0.04 −1.97 −0.31
0.97 0.05 0.76
2.95 ± 1.24 2.76 ± 1.28 2.58 ± 1.46 2.51 ± 1.24 2.34 ± 1.24 2.31 ± 1.17 2.25 ± 1.24 1.97 ± 1.08 1.96 ± 1.17
2.79 ± 1.21 2.66 ± 1.25 2.47 ± 1.42 2.42 ± 1.31 2.13 ± 1.19 2.18 ± 1.19 2.10 ± 1.24 1.81 ± 1.06 1.93 ± 1.22
3.16 ± 1.27 2.88 ± 1.30 2.73 ± 1.52 2.61 ± 1.15 2.60 ± 1.25 2.46 ± 1.11 2.45 ± 1.23 2.16 ± 1.07 2.00 ± 1.09
−1.68 −0.97 −1.03 −0.86 −2.20 −1.36 −1.61 −1.81 −0.35
0.09 0.33 0.31 0.39 0.03* 0.18 0.11 0.07 0.73
Anchors for the ratings of the degree by which prescribers felt antipsychotic polypharmacy was or was not justified based on provided characteristics: 5-point Likert scale: 1= not at all (=0%) 2=a little bit (=25%), 3=somewhat (=50%), 4=a lot (=75%), 5=a whole lot (100% justified) * Not significant after Bonferroni correction; ¶ df=131.
4. Discussion
macy prescribing explaining 24.9% of the variance: respondents who had ‘successfully switched patients to monotherapy’ were significantly less likely to be among the ‘high’ antipsychotic polypharmacy prescribers (OR=0.02, 95% CI: 0.002–0.08, p < 0.0001), whereas those preferring first-generation antipsychotic +first generation antipsychotic combinations (OR=13.86, 95%CI: 3.29–68.50, p < 0.01) and those aiming for a reduction of non-antipsychotic medications (OR=5.46, 95%CI:1.48–21.98, p < 0.013) were more likely among the ‘high’ antipsychotic polypharmacy prescribers (overall model: r2=0.249, p < 0.0001).
This study found that consultant psychiatrists and senior trainees surveyed in Nigeria reported prescribing antipsychotic polypharmacy in over a third of their patients. There were no significant differences based on level of training, likely due to the fact that trainees were generally senior residents and that the composition of the case load in Nigeria does not differ systematically between trainees and consultant psychiatrists. ‘High’ vs. ‘low’ antipsychotic polypharmacy use did not differ significantly based on prescriber characteristics. Similarly, there were no differences regarding reasons against antipsychotic polypharmacy, which were generally rated with higher ratings compared with justification for antipsychotic polypharmacy. Conversely, ‘high’ anti-
Table 3 Prescriber-Rated Lack of Justification for Antipsychotic Polypharmacy. Lack of Justification for Antipsychotic Polypharmacy
Total (n=132)
≤30% (n=73)
> 30% (n=59)
ta
p
Increased risk of chronic side effects Increased risk of acute side effects Potential for drug-drug interaction Increased risk of non-adherence Lack of evidence base High total dose of AP Difficulty determining cause and effect Increased mortality Potential for increased cost
4.32 ± 1.01 4.31 ± 0.98 3.88 ± 1.10 3.87 ± 1.04 3.87 ± 1.18 3.86 ± 1.19 3.82 ± 3.71 3.60 ± 1.37 3.58 ± 1.14
4.34 ± 0.98 4.26 ± 1.05 3.79 ± 1.19 3.82 ± 1.09 3.94 ± 1.16 3.79 ± 1.21 4.11 ± 1.87 3.56 ± 1.38 3.60 ± 1.10
4.29 ± 1.06 4.36 ± 0.89 3.98 ± 0.97 3.93 ± 0.98 3.78 ± 1.20 3.95 ± 1.16 3.45 ± 1.11 3.64 ± 1.36 3.56 ± 1.19
0.28 −0.59 −0.98 −0.61 0.79 −0.74 1.01 −0.36 0.22
0.78 0.56 0.33 0.54 0.43 0.46 0.31 0.72 0.82
Anchors for ratings of how much prescribers globally feel that antipsychotic polypharmacy is problematic: 7-point Likert scale: 1= not at all, 2=minimal, 3=mild, 4=moderate, 5=marked, 6=severe, 7=extreme a df=131.
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2011). Notably, Nigerian prescribers ranked evidence supporting antipsychotic polypharmacy relatively similar independent of the strength of the evidence, making little differentiation between evidence based on case reports, open trials or randomized controlled trials. They ranked clinical wisdom as high as randomized clinical trials. This was not the case in the US and Japanese surveys where clinical wisdom ranked lowest and randomized clinical trials ranked highest, suggesting a potential for educational needs for Nigerian psychiatrists and trainees. In the current survey, prescribers reported that 45% of their patients on antipsychotic polypharmacy could be converted successfully to monotherapy. This was a higher reported conversion rate when compared with the US and Japanese surveys (28% each) (Correll et al., 2011; Kishimoto et al., 2013). This difference could possibly be related to the frequent use of antipsychotic polypharmacy in acute settings to speed up treatment response in Nigeria, rather than its use as an augmentation strategy in refractory patients. In Nigeria, ‘high’ antipsychotic polypharmacy prescribers were less likely to manage patients who they had successfully switched to monotherapy and they were treating more patients in whom they had never attempted a switch to antipsychotic monotherapy. This finding underscores the impact that attitudes may have on actual prescribing practices. However, the opposite could also be true, in that less success prevents clinicians from trying a switch to antipsychotic monotherapy. Lack of a successful switch was reported in 17% of patients in Nigeria compared to 24% in the US and 37% in the Japanese survey (Correll et al., 2011; Kishimoto et al., 2013). Nevertheless, it is surprising that still 27%, 35% and 41% of the patients on antipsychotic polypharmacy in the Nigerian, Japanese and US surveys were reported as not having been tried to revert from antipsychotic polypharmacy to antipsychotic monotherapy, suggesting either some therapeutic inertia or fear of deterioration in patients who are seen as stable or, at least, somewhat improved on an antipsychotic polypharmacy regimen. In fact, the literature on converting patients on antipsychotic polypharmacy to monotherapy suggests that between half and twothirds of patients on antipsychotic polypharmacy can safely and effectively be converted to antipsychotic monotherapy (Tani et al., 2013; Essock et al., 2011; Suzuki et al., 2005, 2004). However, these figures also mean that clinicians attempting such a switch may see worsening in a subgroup of patients, deterring them from attempting such a switch in the future. Clearly, studies are needed that identify patient and treatment characteristics associated with a successful conversion from antipsychotic polypharmacy to antipsychotic monotherapy to help guide clinicians. Our findings should be viewed with the following limitations in mind. First, the sample size was moderate. Second, although recruitment was spread across the country, the non-response rate was high, which may result in a selection bias. Third, the antipsychotic polypharmacy rates reported and views expressed by clinicians may not fully reflect actual practice, as they may provide responses they deemed appropriate as regards published evidence and treatment guidelines. However, we were unable to obtain and link actual prescription data to individual survey respondents. Fourth, there was a skew towards more senior trainees than consultants in the sample, and trainees may be reflecting the views of their trainers or consultants or report practices that have been handed down to them. Finally, information on the diagnoses, target symptoms and severity of illness/impairment of the patients prescribed antipsychotic polypharmacy by the surveyed clinicians was not available nor were data on efficacy and tolerability of antipsychotic polypharmacy or on the views of patients and families assessed in this survey study. This missing data may explain why in our multivariate model, only 25% of the variance between high and low antipsychotic polypharmacy prescribers could be explained. Thus, future studies should aim to both record actual antipsychotic polypharmacy prescription rates of survey respondents and collect information on additional patient and prescriber characteristics that may
psychotic polypharmacy prescribing was significantly associated with the use of first-generation antipsychotic combinations, a lower frequency of a successful conversion of patients from antipsychotic polypharmacy to monotherapy and lack of any previous attempts of switching to antipsychotic monotherapy. Regarding attitudes, ‘high’ antipsychotic polypharmacy prescribers were more likely to endorse the opinion that one antipsychotic was insufficient to prevent a relapse, and believed that antipsychotic polypharmacy will speed up treatment effect. ‘High’ antipsychotic polypharmacy prescription was also often motivated by a desire to reduce the dose of the first antipsychotic as well as reduce the number of non-antipsychotic medications. The reported prevalence of antipsychotic polypharmacy in this study is within the range of rates (7% and 55.4%) obtained from patient audits from previous studies in Nigeria (Adelufosi et al., 2013; Adesola et al., 2013). Compared to similar reports assessing psychiatrists prescription practices for antipsychotic polypharmacy, the frequency was higher than that reported in the United States (17.0%) (Correll et al., 2011) but lower when compared to the frequency from Japan (47.7%) (Kishimoto et al., 2013). The preference for combining first-generation antipsychotics was also reported in one audit in Nigeria (Adelufosi et al., 2013). Conversely, in the US survey, 1.1% of patients were reported to receive two first-generation antipsychotics (Correll et al., 2011), whereas the rate was 17.2% in the Japanese prescriber survey (Kishimoto et al., 2013). The first-generation antipsychotic cotreatment preference may well be reflective of the types of medications available for use by psychiatrists in Nigeria. Since data on extrapyramidal side effects, anticholinergic use, prolactin levels and sexual dysfunction were unavailable, it is unclear to what degree this practice in Nigeria is associated with these adverse effects. Although second generation antipsychotics are now more readily available in Nigeria and other parts of Africa, they are usually more expensive and cannot be afforded by the majority of patients who pay for their care ‘out-ofpocket’. Unlike in other settings in Europe, North America and some countries in Asia where health insurance schemes provide coverage for large sections of the mentally ill, a vast majority of patients rely on their relatives to pay for care, particularly when they are unable to work due to the severity of their mental illness. Future studies in this setting are needed to explore the impact that limited access to an array of medications have on the prescribing habits of psychiatrists in the Nigeria. In the US, Japanese and Nigerian surveys ongoing cross-titration and failure or intolerance to clozapine were consistently among the highest rated reasons justifying antipsychotic polypharmacy. However, in the Nigerian survey, a different route of administration and different pharmacological mechanisms ranked not as high as in the Japanese and the US survey, which may also have to do with a more restricted psychiatric medication armamentarium. Conversely, reducing the number of non-antipsychotic medications was seen as a particular advantage by ‘high’ antipsychotic polypharmacy users in Nigeria, whereas this focus did not differentiate ‘high’ and low’ antipsychotic polypharmacy users in the other two similar surveys (Correll et al., 2011; Kishimoto et al., 2013). Whether clinicians in Nigeria try reserving other, potentially more expensive medications by combining two first-generation antipsychotics or whether they are attempting to delay use of benzodiazepines with abuse potential, by adding a low potency to a high potency first-generation antipsychotic, is suggested by the fact that chlorpromazine was one of the first-generation antipsychotics in the three most utilized combinations. This potential reason for this finding is unclear and should be examined further. Interestingly, ‘high’ antipsychotic polypharmacy users also reported that one goal of antipsychotic polypharmacy was to speed up the effect of medications. In Nigeria, as in other low and middle income countries, individuals with psychotic disorders present late to services and often with severe symptoms. Due to constraints for bed spaces and treatment costs, psychiatrists may therefore prefer combining antipsychotics hoping to hasten treatment response and discharge (James, 138
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monotherapy. Am. J. Psych. 168 (7), 702–708. Falkai, P., Wobrock, D.T., Lieberman, J., Glenthoj, B., Gattaz, W.F., Möller, H.J., 2009. World federation of Societies of biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, Part 1: acute treatment of schizophrenia. World J. Biol. Psychiatry. Fleischhacker, W.W., Uchida, H., 2012. Critical review of antipsychotic polypharmacy in the treatment of schizophrenia. Int. J. Neuropsychopharmacol. 17 (07). Gallego, J.A., Bonetti, J., Zhang, J., Kane, J.M., Correll, C.U., 2012a. Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009. Schiz. Res. 138 (1), 18–28. Gallego, J.A., Nielsen, J., De Hert, M., Kane, J.M., Correll, C.U., 2012b. Safety and tolerability of antipsychotic polypharmacy. Expert Opin. Drug Saf. 11 (4), 527–542. Iasevoli, F., Buonaguro, E.F., Marconi, M., Di Giovambattista, E., Rapagnani, M.P., De Berardis, D., Valchera, A., 2014. Efficacy and clinical determinants of antipsychotic polypharmacy in psychotic patients experiencing an acute relapse and admitted to hospital stay: results from a cross-sectional and a subsequent longitudinal pilot study. ISRN Pharm. 762127. Ito, H., Koyama, A., Higuchi, T., 2005. Polypharmacy and excessive dosing: psychiatrists' perceptions of antipsychotic drug prescription. Br. J. Psych. 187 (3), 243–247. James, B.O., 2011. Rapid tranquillization agents for severe behavioural disturbance: a survey of African psychiatrists' prescription patterns. Trop. Dr. 41 (1), 49–50. Kishimoto, T., Watanabe, K., Uchida, H., Mimura, M., Kane, J.M., Correll, C.U., 2013. Antipsychotic polypharmacy: a Japanese survey of prescribers' attitudes and rationales. Psych. Res. 209 (3). Koen, L., Magni, P., Niehaus, D.J., le Roux, A., 2008. Antipsychotic prescription patterns in Xhosa patients with schizophrenia or schizoaffective disorder. Afr. J. Psych. 11 (4), 287–290. Li, Q., Xiang, Y.-T., Su, Y.-A., Shu, L., Yu, X., Chiu, H.F., Si, T.M., 2015. Antipsychotic polypharmacy in schizophrenia patients in China and its association with treatment satisfaction and quality of life: findings of the third national survey on use of psychotropic medications in China. Aust. N. Z. J. Psych.. Lochmann van Bennekom, M.W.H., Gijsman, H.J., Zitman, F.G., 2013. Antipsychotic polypharmacy in psychotic disorders: a critical review of neurobiology, efficacy, tolerability and cost effectiveness. J. Psychopharmacol. 27 (4), 327–336. Sernyak, M.J., Rosenheck, R., 2004. Clinicians' reasons for antipsychotic coprescribing. J. Clin. Psych. 65 (12), 1597–1600. Suzuki, T., Uchida, H., Takeuchi, H., Nomura, K., Tanabe, A., Watanabe, K., Yagi, G., H, K., 2005. Simplifying psychotropic medication regimen into a single night dosage and reducing the dose for patients with chronic schizophrenia. Psychopharmacol. (Berl.). 181 (3), 566–575. Suzuki, T., Uchida, H., Watanabe, K., Yagi, G., Kashima, H., 2004. A clinical case series of switching from antipsychotic polypharmacy to monotherapy with a secondgeneration agent on patients with chronic schizophrenia. Prog. NeuroPsychopharmacol. Biol. Psych. 28 (2), 361–369. Tani, H., Uchida, H., Suzuki, T., Fujii, Y., Mimura, M., 2013. Interventions to reduce antipsychotic polypharmacy: a systematic review. Schiz. Res. 143 (1), 215–220. Taylor, D.M., Smith, L., Gee, S.H., Nielsen, J., 2012. Augmentation of clozapine with a second antipsychotic - a meta-analysis. Acta Psych. Scand. 125 (1), 15–24. Tsutsumi, C., Uchida, H., Suzuki, T., Watanabe, K., Takeuchi, H., Nakajima, S., Kapur, S., 2011. The evolution of antipsychotic switch and polypharmacy in natural practice–a longitudinal perspective. Schizo. Res. 130 (1–3), 40–46.
explain antipsychotic polypharmacy prescription behaviour. In summary, our findings identify relevant prescriber characteristics that differentiate ‘high’ from ‘low’ antipsychotic polypharmacy users. These results can inform educational campaigns and performance improvement projects, namely the guided attempt at converting patients successfully from antipsychotic polypharmacy to antipsychotic monotherapy. Going forward, identifying interventions to reduce antipsychotic polypharmacy prescribing among psychiatrists are desirable. As earlier reported, education is considered a passive and relatively ineffective intervention, rather, active interventions have shown some promise (Fleischhacker and Uchida, 2012). Actual prescription monitoring and feedback significantly reduced antipsychotic polypharmacy prescribing. However, the feasibility of such interventions in a low income setting is debatable because of poor and ineffective health system monitoring and the absence of locally relevant guidelines. Future studies should explore what strategies may be effective in reducing high antipsychotic polypharmacy prescribing, which should only be an option of last resort, and in which subgroups of patients antipsychotic polypharmacy may be useful or needed (Essock et al., 2011; Tani et al., 2013). References Adelufosi, A., Abayomi, O., Tolulope, O., 2013. Antipsychotic polypharmacy and excessive dosing in Nigerian patients with schizophrenia: prevalence, correlates and relationship with quality of life. Biol. Psych. 73 (9), 213S. Adesola, A., Anozie, I., Erohubie, P., James, B., 2013. Prevalence and correlates of ‘high dose’ antipsychotic prescribing: findings from a hospital audit. Ann. Med. Health Sci. Res. 3 (1), 62–66. Barbui, C., Signoretti, A., Mulè, S., Boso, M., Cipriani, A., 2009. Does the addition of a second antipsychotic drug improve clozapine treatment? Schiz. Bull 35 (2), 458–468. Chang, J., Kim, B., 2014. A survey study of the satisfaction and attitude of the Korean psychiatrists toward antipsychotic polypharmacy. Ann. Clin. Psych. 26 (1), 64–69. Correll, C.U., Gallego, J.A., 2012. Antipsychotic polypharmacy: a comprehensive evaluation of relevant correlates of a long-standing clinical practice. Psych. Clin. N. Am. 35 (3), 661–681. Correll, C.U., Rummel-Kluge, C., Corves, C., Kane, J.M., Leucht, S., 2009. Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schiz. Bull. 35 (2), 443–457. Correll, C.U., Shaikh, L., Gallego, J.A., Nachbar, J., Olshanskiy, V., Kishimoto, T., Kane, J.M., 2011. Antipsychotic polypharmacy: a survey study of prescriber attitudes, knowledge and behavior. Schiz. Res. 131 (1–3), 58–62. Essock, S.M., Schooler, N.R., Stroup, T.S., McEvoy, J.P., Rojas, I., Jackson, C., Covell, N.H., 2011. Effectiveness of switching from antipsychotic polypharmacy to
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