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J Clin Psychopharmacol. Author manuscript; available in PMC 2021 February 11.
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Published in final edited form as:

J Clin Psychopharmacol. 2020 ; 40(6): 541–552. doi:10.1097/JCP.0000000000001282.

Antipsychotic Medication in Sub-Saharan Africa: A Systematic

Literature Review
Sanjana Kumar, Shwetha Sudhakar, Martha Sajatovic, Jennifer B Levin
1.Case Western Reserve University School of Medicine, Cleveland, OH

Abstract
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Objective: Schizophrenia is a treatable psychiatric condition affecting millions of people

worldwide. However, there is limited evidence on the use of antipsychotic medications in certain
areas of the world, such as Sub-Saharan Africa (SSA). The aims of this systematic literature
review were to find papers focused on the use of antipsychotic drugs for treatment of individuals
with primary psychotic disorders in SSA, to describe the origin and timeline of published reports,
to assess the methodological quality of intervention outcome studies, to summarize the
intervention strategies, to examine patient level outcomes, and to analyze temporal trends in study
methodology over the observation window.

Methods: Pubmed, PsychInfo, Cochrane Collaboration, and CINAHL databases were searched
to locate studies conducted in SSA that focused on antipsychotic medication treatment for primary
psychotic disorders and that investigated at least one patient level outcome. Articles written in
English and published in peer-reviewed journals before April 2019 were included.
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Epidemiological studies, drug discontinuation studies, studies with drugs other than
antipsychotics, and multi-center studies that did not specify SSA results were excluded. The
authors used a standardized instrument to rate studies’ methodological quality.

Results: Twenty six articles were reviewed. Based on studies’ methodological quality, three
levels of evidence were found: single-group reports, quasi-experimental studies, and randomized
controlled trials. Studies chosen analyzed the associations of antipsychotics with either
improvement in psychiatric symptoms, presence of side effects, rates of remission, or
improvement in functional status. Nine studies reported improvements in psychiatric symptoms
associated with receiving an antipsychotic medication. Seven studies investigating side effects of
antipsychotics found that they were associated with an increase in metabolic syndrome. Two
studies reported that remission was achieved in the majority of subjects treated with
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antipsychotics, and one study reported improvements in functional status associated with receiving
an antipsychotic.

Conclusions: Although the results suggest that, despite side effects, treatment with
antipsychotic medications may be beneficial for individuals with primary psychotic disorders in
SSA, several gaps were identified in the current literature. There is a scarcity of research on
antipsychotics from countries in sub-Saharan Africa apart from South Africa. Moreover, the

Previous Presentation:
This paper has not been previously published or presented, and is not under consideration by any other journal.
 Kumar et al. Page 2

underrepresentation of persons from racial or ethnic minority groups in this literature limits its
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generalizability. The implications for research and practice are discussed.

INTRODUCTION
Schizophrenia affects more than 20 million people worldwide and people with schizophrenia
are 2-3 times more likely to die prematurely compared to the general population.1
Schizophrenia and other psychotic disorders are defined by abnormalities which affect
quality of life such as delusions, hallucinations, disorganized thinking, grossly disorganized
or abnormal motor behavior and negative symptoms.2 According to the World Health
Organization, more than 69% of people with schizophrenia are not receiving appropriate
care and 90% of people with untreated schizophrenia live in low- and middle- income
countries, such as the countries in Sub-Saharan Africa (SSA). Lack of access to mental
health services is an important issue in SSA and lower-and middle income countries more
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broadly.1

In spite of the existing level of burden in many settings, schizophrenia is a treatable

condition responsive to evidence-based treatments such as antipsychotic medications. There
is however, a limited evidence base on the use of antipsychotic treatment for schizophrenia
in SSA. Past reviews of the literature have focused mainly on the different types of treatment
available. In a 2017 literature review of forty studies from eight countries, Chidarikire et al.
concluded that people living with schizophrenia in SSA were mainly treated by faith,
traditional healers and modern psychiatry, if treated at all.3 A 2015 literature review by
Burns et al. found that approximately half of individuals seeking formal health care for
mental disorders in Africa from 1990 to 2004 chose traditional and religious healers as their
first-line treatment.4 There is a paucity of information that identifies and characterizes use of
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antipsychotic medications and their effects on patients with schizophrenia or other psychotic
disorders in SSA. This systematic literature review of original research articles focused on
the use of antipsychotic drugs for treatment of individuals with schizophrenia/primary
psychotic disorders in SSA describes the origination and timeline of published reports,
assesses the methodological quality of antipsychotic intervention outcome studies,
summarizes the intervention strategies, examines patient level outcomes including
information on racial and ethnic minority sub-groups and analyzes temporal trends in study
methodology over the observation window.

METHODS
Study Selection
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We searched the Pubmed, PsychInfo, Cochrane Collaboration and CINAHL databases for
original antipsychotic outcome studies and clinical trials published up until April 2019. Our
search strategy included combinations of the following key words: schizophrenia,
schizoaffective disorder, psychosis, severe mental illness, chronic psychotic conditions,
antipsychotic medication, antipsychotic, medication treatment, clinical trial, sub-Saharan
Africa, and the individual countries of sub-Saharan Africa. We also did an African Journals
Online search using the syntax schizophrenia for the first term and treatment, antipsychotic
medication, antipsychotic, clinical trial, or medication treatment for the second term.

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Our search yielded a total of 883 results, with a new total of 709 articles after removing 174
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duplicates. The first two authors (SK and SS) screened all abstracts for relevance and found
129 pertinent articles. We then narrowed down the inclusion criteria to studies investigating
primary psychotic disorders (including schizophreniform, schizoaffective, schizophrenia,
and bipolar disorder), primary treatment with one or more antipsychotic medications, and at
least one patient level outcome (for example, psychiatric symptoms, functional status,
adherence, and side effects). We excluded epidemiological studies, drug discontinuation
studies, studies with drugs other than antipsychotics, and multi-center studies that did not
specify SSA results.

To ensure that the inclusion/exclusion criteria were being applied in the same way, three of
the authors performed a dry run of abstract review. The first ten abstracts from PubMed and
PsychInfo each were compiled into an Excel spreadsheet and the authors decided
independently whether or not to include the articles. We compared our decisions and came
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to a consensus regarding any discrepancies. We then applied these uniform criteria to the rest
of the articles, excluding 84 articles. Forty-five full text articles were screened to remove
non-prospective studies and confirm the location of the studies. In total, 26 articles were
included in the review. Figure 1 shows the publication review process.

Analytical Strategies
A data extraction checklist was developed to systematically code study characteristics
including author, year, country, study design, sample description, control group, treatment,
outcome measurement, and results.5 To rate the methodological quality of studies, we
employed a modified version of the Methodological Quality Rating Scale (MQRS).6 This
rating scale assesses the methodological quality of studies across 12 different dimensions
(for example, study design and follow-up length). Cumulative MQRS scores for each study
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range from 1, poor quality, to 16, high quality. Working together, the first two authors (SK
and SS) used the modified MQRS to rate the methodological rigor of each of the 26 studies
included in this review.

RESULTS
Overview
Table 1 displays the characteristics of the 26 studies included in the final review. Study
samples ranged in size from 12 to 207, with an average sample size of 207. 12 studies had a
sample size between 12 and 50, 9 studies had a sample size between 51 and 150, and 5
studies had a sample size between 151 and 207.
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Studies were from Nigeria (n=3), South Africa (n=21), Malawi (n=1), and 1 multi-center
study in Nigeria and South Africa. Most studies were published between 2015 and 2019,
with 5 studies published in 2015 and 2017 (Figure 2).

Designs
Out of 26 total studies, 15 were single group pre-test post-test studies, 5 were quasi-
experimental studies with non-equivalent control groups, and 6 were randomized controlled

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studies. There were 5 studies that compared two different antipsychotic medications to each
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other, and those were considered randomized controlled studies in our analysis. S. Brook et
al. 1998 compared haloperidol to zuclopenthixol acetate while Emseley et al. 2004 and
Emsley et al. 2005 compared haloperidol to quetiapine.789 Emsley et al. 2015 compared
risperidone to flupenthixol decanoate in 2 different studies.2223 In addition, there was 1
study, Landmark et al. 1994, that compared fluphenazine decanoate depot alone to
fluphenazine decanoate with HCl, which was also considered a randomized controlled study
in our analysis.10

Out of 26 total studies, 9 studies were blinded and 25 were single site studies. The only
multisite study was Ojagbemi et al. 2018 which involved data from both South Africa and
Nigeria.11

Funding
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The top three sponsors for the studies in this review were the Medical Research Council of
South Africa, the New Partnership for Africa’s Development (NEPAD), and Lundbeck
International. Out of 26 total studies, 12 received funding from the Medical Research
Council of South Africa; 10 received funding from NEPAD; and 6 received funding from
Lundbeck International. There were 2 studies that were funded completely by their authors,
and 2 studies that were funded by an academic institution, the University of Stellenbosch. A
variety of pharmaceutical companies provided funding, such as Janssen (for 2 studies),
Pfizer Incorporated (for 1 study), and Bristol Myers Squibb (for 1 study). With regard to
government funding, there was 1 study that assessed patients in a federal government funded
hospital in the South-East region of Nigeria, and another study that was provided funding
from the Office of the US Global AIDS Coordinator and the US Department of Health and
Human Services. The National Research Foundation of South Africa and the Discovery
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Foundation provided funding for 1 study each. In addition, Harry Crossley and MATRICS
Assessment Inc. provided funding for 1 study each. Lastly, 1 study stated that the authors
received no specific grant from any funding agency, commercial or not-for-profit sector.

Populations
Gender—All of the studies reported the gender make-up of the sample groups. The
samples were predominantly male, and two studies consisted of a sample with a female
majority.1213

Racial and Ethnic Groups—17 (65.4%) studies reported the racial demographics of the
samples. The total sample size across these 17 studies was 1158: 263 (22.7%) were black,
769 (66.4%) were mixed, and 126 were white (10.9%).
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2 studies listed the ethnic makeup of their samples. Landmark’s sample consisted of 93
Xhosa patients whereas Ojagbemi had 81 Yoruba patients and 18 Xhosa patients.1011

Racial and ethnic differences in treatment outcomes were not examined in any of the studies.

Diagnosis—Out of 26 total studies, 24 had samples with patients who were diagnosed
with either schizophrenia or schizophreniform disorder. Three of these studies also included

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patients with bipolar disorder. 2 studies stated that their sample patients experienced first-
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episode psychosis and didn’t identify a specific psychotic disorder.

Antipsychotics
Out of 26 total studies, 6 did not clarify which antipsychotics were administered. Ten studies
utilized flupenthixol decanoate, 5 studies utilized risperidone, 6 studies utilized haloperidol,
2 studies utilized quetiapine, 1 study utilized zuclopenthixol acetate, and 1 study utilized
ziprasidone.

Outcomes
Psychiatric Symptoms—9 studies looked at psychiatric symptoms as an outcome
measure of antipsychotics, with 6 studies specifying using the Positive and Negative
Syndrome Scale (PANSS), 1 study using the Brief Psychiatric Rating Scale (BPRS) and
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Clinical Global Impression of Severity (CGS)14, and the other 2 studies not specifying the
measure used. In a prospective cohort study by Oosthuizen in 2001, 35 patients with a first
episode of psychosis were treated with Haloperidol for 12 weeks, restricting the dose to 1
mg for the first 4 weeks.15 The mean percentage reduction in Positive and Negative
Symptom Scale score between baseline and 6 and 12 weeks was 30.3% (SD 20.9%) and
41.4% (SD 16.6%), respectively.15 In a prospective cohort study by Ezeme et al, out of 172
schizophrenia patients treated with typical and atypical antipsychotics for 6 weeks, 68% had
a 20% or more reduction in PANSS.13

Studies comparing different treatments found no difference in PANSS between 2 mg and 8

mg of haloperidol16 and no difference in BPRS and CGS scores between haloperidol and
zuclopenthixol acetate.7 One particular study found that treatment reduction was associated
with reduction of psychiatric symptoms.17 In a prospective cohort study conducted in South
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East Nigeria, good medication adherence, good premorbid functioning, fewer negative
symptoms, less cognitive impairment, absence of comorbid personality disorder, and short
duration of untreated psychosis were associated with a greater reduction in psychiatric
symptoms.18 In another prospective cohort study by Emsley, 31 patients were treated with
long acting risperidone injectable for a first and second episode of schizophrenia, and no
difference in PANSS was found between the two treatments.19

Side Effects—Eight studies investigated side effects as an outcome of antipsychotics,

primarily looking at metabolic syndrome and extrapyramidal symptoms. Most studies found
that antipsychotics were associated with an increase in metabolic syndrome, but a
prospective randomized parallel group study by Emsley et al comparing quetiapine and
haloperidol found no significant metabolic changes from baseline in either group.9 A
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prospective cohort study by Chiliza that looked at 107 largely antipsychotic naive first
episode schizophrenia patients found significant increases in BMI (p<.0001), waist
circumference (p=.0006), and triglycerides (p=0.03) and a significant decrease in HDL
(p=.005). However, no changes were seen in systolic and diastolic pressure, glucose, and
cholesterol values over time. Furthermore, the change in BMI was correlated with the
change in triglycerides.20

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Studies specifying tardive dyskinesia as a side effect found that patients with tardive
dyskinesia were older and received higher mean doses of haloperidol21 and that between
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quetiapine and haloperidol, treatment with quetiapine was associated with a significantly
greater improvement in tardive dyskinesia.8 An early prospective cohort study by
Oosthuizen suggests that the dose of haloperidol is important in determining side effects.
Oosthuizen found that there was no significant difference in EPS from baseline in patients
treated with 1 mg of haloperidol over 12 weeks.15 A 2004 study by Oosthuizen further
clarified that a 2 mg dose of haloperidol over 6 weeks was associated with fewer
extrapyramidal side effects (EPS) than a 6 mg dose.16 Lastly, a prospective cohort study that
looked at treatment with low dose flupenthixol decanoate for 3 months recorded treatment
induced EPS in 38.6% of patients, and found that spontaneous EPS was associated with
treatment emergent akathisia in patients with a longer duration of untreated psychosis.11

Between 2015 and 2017, Emsley et al published three studies looking at changes in brain
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volume on MRI as a side effect of antipsychotic medication. No other publication mentioned

brain volume as a possible side effect. When comparing 22 never-treated patients with a first
episode of schizophrenia who were treated with risperidone or flupentixol decanoate with 23
matched healthy controls over 13 weeks, Emsley found that caudate sizes were larger at
baseline in patients and that there was no significant association between caudate volume
and improvement in psychotic symptoms.22 Another paper published in the same year
conducted different analyses on the data and noted that ventral diencephalon volume
reduction was strongly correlated bilaterally with body mass increase and HDL-cholesterol
reductions, and unilaterally with blood glucose elevation; there were no significant changes
in pre-cortical thickness.23 However in 2017, in another prospective cohort study comparing
23 first episode patients on flupentixol decanoate with 53 healthy controls, Emsley observed
excessive cortical volume reductions in patients [−4.6 (6.6)%] v. controls [−1.12 (4.0)%] (p
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= 0.009), with no significant group differences for changes in subcortical grey matter and
white matter volumes. Furthermore, there was no significant association between cortical
volume changes and psychopathology, functionality, duration of untreated psychosis or EPS.
24

Remission—3 studies considered remission as a possible outcome.192526 A prospective

cohort study in Malawi looked at outcomes in 126 first episode psychosis patients treated
with antipsychotic medication for 18 months. Using the Remission in Schizophrenia
Working Group criteria, 71.4% of patients achieved symptomatic remission with a mean
duration of 8.05 months. A number of factors delayed symptomatic remission, including
being male, family history of psychiatric disorders, deteriorating premorbid functioning, and
being separated/divorced/widowed.25 In Emsley’s prospective cohort study looking at
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treatment of 50 newly diagnosed patients with ILAR for 2 years, 64% of the patients
achieved remission.26 In a 2013 study by Emsley looking at 2 different treatment periods of
31 patients, remission rates were similar for both treatment periods.19

Functional Status—Only one study primarily investigated functional status. Olivier et al

analyzed changes in the MATRICS Cognitive Consensus Battery (MCCB) score over 12
months between 92 patients with first episode schizophrenia and 100 healthy controls. Using

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a mixed-effects model, patients had a greater change in MCCB composite score than
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controls. There were significant group x time effects for attention and vigilance, visual
learning, verbal learning, and working memory.27

DISCUSSION
Aims of Study
Sub-Saharan Africa has a high burden of mental illness, and antipsychotic medications are
essential in treatment. The goal of this study was to provide a systematic literature review of
antipsychotic medications tested in sub-Saharan Africa. We found 26 studies, focusing our
review on a few key aspects.

Our first aim was to study the origination and timeline of published reports. While the
majority of reports were from South Africa, perhaps not surprising given that South Africa is
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a higher-income nation, only three (11.5%) reports included countries outside of South
Africa. A review of poverty and common mental disorders in 2010 looked at several low and
middle income countries, including many in SSA, and found positive associations between
poverty and mental illness.28 Thus, the paucity of research on antipsychotics from other
countries in sub-Saharan Africa is surprising, and suggests a gap in evidence that needs to be
addressed.

Another aim was to examine the inclusion of people from racial and ethnic minority groups.
Only two studies mentioned ethnic groups among Black South Africans, mentioning Xhosa
patients. While both studies used interviewers speaking Xhosa, no other ethnic groups were
specified. South Africa is home to people of various ethnicities such as Zulu, Basotho, and
Bapedi,29 and thus attention to cultural elements when implementing an antipsychotic
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intervention can affect outcomes.

Our third aim was to rate studies’ methodological quality. The findings from the MQRS
ratings suggest three levels of evidence corresponding to the degree of internal validity of
the studies. At the lowest level were the fifteen uncontrolled studies that relied on single-
group pre-post designs. These studies tended to not be blinded (N=87%). At the second level
of evidence were the five studies that utilized quasi-experimental methods. More than half of
these quasi-experimental studies (N=60%) didn’t enumerate the number of dropouts. Similar
to the uncontrolled trials in level 1, most of the studies were not blinded (N=80%).

At the highest level of methodological quality were three randomized controlled studies. The
three studies that score the highest number of points were Emsley et al. 2005, Emsley et al.
2004, and Brook et al. 1998.789 These blinded studies all had 44-45 patients, all used
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standardized interventions, and treatment ranged from 4 weeks to 52 weeks. Two major
limitations of these randomized controlled trials was that two had follow up rates less than
70% and all three studies failed to use collateral verification of patient’s self reports. Future
randomized controlled trials in this area should consider employing techniques to improve
follow up rate. In addition, future studies should acquire objective measures to verify patient
reports to strengthen the validity of the results.

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Our fourth aim was to analyze how the types of studies being conducted in SSA have
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changed over time. Firstly, sample size generally increased. Secondly, earlier studies seem to
focus on psychological symptoms as outcome measures, using BPRS and PANSS as
standardization for these symptoms. Later studies focused more explicitly on side effects,
such as extrapyramidal symptoms. This might be related to the fact that some side effects,
such as weight gain or metabolic syndrome might be more likely to become obvious with
longer exposure to treatment and greater clinician (and researcher) awareness of these side
effects. That being said, the treatment follow-up length for the studies we reviewed has
stayed relatively consistent over time with 15 studies lasting 12 months or longer and 10
studies lasting less than 6 months. There does not appear to be any significant trend towards
conducting studies with longer treatment follow-up times.

Our final aim was to examine intervention strategies. Across the studies reviewed, the goal
of antipsychotic intervention was to treat schizophrenia, schizophreniform disorder, or first
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episode psychosis. Interventions included first generation antipsychotic medications such as

haloperidol, zuclopenthixol, and flupenthixol decanoate; and second generation
antipsychotic medications such as quetiapine, ziprasidone, risperidone. There were 5 studies
that compared two different antipsychotic interventions. Brook et al. 1998 compared
haloperidol to zuclopenthixol acetate and found that there were no significant differences
between the two agents in efficacy or tolerability.7 Emsley et al. 2004 compared haloperidol
to quetiapine and found that quetiapine resulted in greater improvements in dyskinesia and
fewer EPS.8 Emsley et al. 2005 compared the same two medications and found that there
were no differences in BMI or HBA1c between the two medications; BMI and HBA1c are
measures of metabolic syndrome, a common side effect of antipsychotics.9 Emsley et al.
2015 compared risperidone to flupenthixol decanoate in 2 different studies and no
differences between the two were found with regards to brain volume on MRI.2223
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Landmark et al. 1994, compared fluphenazine decanoate depot alone to fluphenazine

decanoate with HCl, and found that the combined treatment significantly shortened the
length of hospital stay from a mean of 40.7 days to a mean of 30.5 days; the combined
treatment group also obtained significantly higher improvement ratings one week after the
start of treatment than the single treatment patients.10

Limitations
Our review has several limitations. Since one of the inclusion criteria in this review was that
reports be published in English, key findings in other languages may not have been captured.
Moreover, the difference in outcome measures (especially with psychiatric symptoms and
extrapyramidal symptoms), small samples, and different antipsychotics used prevented us
from conducting a meta-analysis. In any systematic literature review, there is the possibility
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of missing published studies that meet the preset inclusion criteria, so we utilized multiple
databases and manual searches to reduce this possibility. Finally, it is important to note that
no measurement technique is free of error. To minimize errors in our ratings of the studies’
methodological qualities, we used an established measuring system, MQRS scoring, and
rated all studies together, resolving any disagreements in a standardized manner.

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CONCLUSIONS
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In conclusion, there is a very limited literature on antipsychotic treatment for chronic

psychotic disorders in SSA. While symptoms are reduced with both first and generation drug
treatments, side effects can be substantial and rates of adherence are often sub-optimal.
Given the extensive burden of chronic psychosis on patients and families there is a critical
need for additional studies that identify best practices and therapeutic options in this setting.

Acknowledgments
Sources of Support:

This study was supported by a grant from the National Institute of Mental Health (NIMH) MH114700 (PIs
Sajatovic and Mwambo). Its contents are solely the responsibility of the authors and do not necessarily represent the
views of the NIMH.
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Conflict of Interest Declaration:

Dr. Martha Sajatovic has received grants from Otsuka, Alkermes, Janssen, International Society for Bipolar
Disorders, Reuter Foundation, Woodruff Foundation, Reinberger Foundation, National Institutes of Health (NIH),
and the Centers for Disease Control and Prevention (CDC) in the past three years, is a consultant for Alkermes,
Bracket, Otsuka, Janssen, Neurocrine, Health Analytics, Frontline Medical Communications, has received royalties
from Springer Press, Johns Hopkins University Press, Oxford Press, UpToDate; and has participated in American
Physician’s Institute, MCM Education, CMEology, Potomac Center for Medical Education, Global Medical
Education, Creative Educational Concepts, and Psychopharmacology Institute. Other authors have nothing to
disclose.

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Highlights:
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• This paper reviews 26 studies conducted in SSA that focused on antipsychotic

medication treatment for primary psychotic disorders and that investigated at
least one patient level outcome.

• Studies chosen analyzed the associations of antipsychotics with either

improvement in psychiatric symptoms, presence of side effects, rates of
remission, or improvement in functional status.

• Nine studies reported improvements in psychiatric symptoms associated with

receiving an antipsychotic medication; seven studies investigating side effects
of antipsychotics found that they were associated with an increase in
metabolic syndrome; two studies reported that remission was achieved in the
majority of subjects treated with antipsychotics; and one study reported
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improvements in functional status associated with receiving an antipsychotic.

• Antipsychotic medications may be beneficial for individuals with primary

psychotic disorders in SSA, however there is a scarcity of research on
antipsychotics from countries in sub-Saharan Africa apart from South Africa.
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Figure 1:
PRISMA Flowchart for Publication Review Process
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 Kumar et al. Page 14
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Figure 2:
Number of Publications Published per Year
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Table 1:

Characteristics of Studies Included in Review

Author/Year Country Study Design Sample Description Control Treatment Outcome Measurement Results
Kumar et al.

Luckhoff et al. South Prospective 106 minimally treated or flupenthixol Psychopathology treatment duration predicted improvement in
2019 Africa Cohort antipsychotic-naive decanoate over 12 evaluated using the psychopathology independent of age, sex,
patients months Positive and Negative ethnicity, substance use
Syndrome Scale
(PANSS)

Ojagbemi et al. South Prospective 99 Xhosa (South Africa) flupenthixol Neurological soft signs EPS recorded in 34 patients (38.6%). Akathisia
2018 Africa and Cohort and Yoruba (Nigeria) decanoate for 3 (NSS) and in patients with a longer duration of untreated
Nigeria months extrapyramidal psychosis (r = 0.75, β = 0.70, p = 0.008).
symptoms (EPS) Association specific for parkinsonism (r = 0.75,
β = 0.85, p = 0.008) and dyskinesia (r = 0.75, β =
1.70, p = 0.008).

Ezeme et al. Nigeria Prospective 172 patients with antipsychotics for 6 Improvement defined as Better response associated with medication
2017 Cohort schizophrenia weeks ≥ 20% reduction in adherence, good premorbid functioning, fewer
PANSS negative symptoms, less cognitive impairment,
less co-morbidity, and short duration of untreated
psychosis.

Ezeme et al. Nigeria Prospective 172 patients with antipsychotics for 6 Improvement defined as 68% had a good response while 32% had poor
2016 Cohort schizophrenia weeks ≥ 20% reduction in response.
PANSS

Olose et al. Nigeria Prospective 60 antipsychotic naive 60 first- antipsychotics for 12 Fasting lipid profiles at Mean endpoint of total cholesterol/lipids
2017 Cohort patients with degree weeks baseline and after 12 significantly higher than initial values.
schizophrenia relatives weeks Prevalence of dyslipidemia 13%. Patients on
matched atypical antipsychotics had higher risk for
for gender dyslipidemia.
and age

Emsley et al. South Prospective 126 patients with first- standardized Neurological Evaluation Significant effects for all NSS domains.
2017 Africa Cohort episode psychotic antipsychotics for 12 Scale (NES); Improvements in sensory integration predicted
disorder months State- and trait-related by working memory (p=0.01); Improvements in
associations with motor sequencing predicted by working memory
psychopathology, and (p=0.005) and functionality (p=0.005); NES total
functionality change predicted by disorganised symptoms
(p=0.02). More substantial associations between

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trait-related vs. state-related change.

Chiliza et al. South Prospective 126 patients with chronic flupenthixol Psychiatric Symptoms 12% non-responders. Non-responders were
2015 Africa Cohort psychotic disorders decanoate for 12 younger, had more disorganised symptoms,
months poorer functioning, lower quality of life, more
prominent neurological soft signs (NSS) and
lower BMI.

Chiliza et al. South Prospective 207 patients with first flupenthixol Adherence, Psychiatric 72% completed 12 months of treatment. Good
2016 Africa Cohort episode schizophrenia decanoate for 12 Symptoms, Functional acceptance, tolerability and adherence to depot.
months Status; 82% responded to treatment, 60% remitted.
Quality of life, Relapse in 19%, and 5% were treatment
Medication tolerability resistant.
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Author/Year Country Study Design Sample Description Control Treatment Outcome Measurement Results
Emsley et al. South Prospective 31 patients treated for 2-year treatment with PANSS PANSS and overall response rates similar for the
2013 Africa Cohort first and second episodes risperidone long- 2 treatment periods. 55% second episode patients
of psychosis acting injection discontinued the study compared with 28% first
(RLAI) for a first episode, suggesting reduced effectiveness after
episode and 2-year illness recurrence. Non-responsiveness in 16%,
Kumar et al.

further treatment consistent with the hypothesis that relapse may

phase for a be biologically harmful in a subset of patients.
recurrence episode

Emsley et al. South Prospective 50 newly diagnosed long-acting injectable Remission Remission achieved in 64%. Of those achieving
2008 Africa Cohort patients with risperidone for 2 remission, 97% maintained this status until study
schizophrenia or years completion.
schizophreniform
disorder aged 16 to 43

Emsley et al. South Prospective 50 patients aged 15 to 43 long-acting injectable Remission; EPS; 36 patients (72%) completed the trial. Of 39
2008 Africa Cohort years with newly risperidone for 2 prolactin levels (78%) who showed clinical response of 50%, 4
diagnosed years relapsed. 32 (64%) remitted. 10 patients required
schizophreniform anticholinergic medication, 1 developed
disorder or schizophrenia dyskinesia. Prolactin levels were elevated in 18
(50%). Mean increase in BMI was 4.8 kg/m (SD,
3.8 kg/m).

Oosthuizen et South Prospective 57 subjects with first- haloperidol for 12 Psychiatric Symptoms; Twelve-month incidence of tardive dyskinesia
al. 2003 Africa Cohort episode psychosis months Side Effects (TD) was 12.3% (N = 7). TD patients were older
(p = .01) and received higher doses of
haloperidol (p = .004). Age (p = .031), negative
symptoms (p = .028), and dose of haloperidol (p
= .016) were predictors of TD risk.

Brook S. 2000 South Prospective 12 patients with acute Short term Brief Psychiatric Rating Improvements in BPRS and CGI maintained on
Africa Cohort exacerbation of intramuscular (IM) Scale (BPRS) and days 4 and 5. No extrapyramidal syndrome or
schizophrenia ziprasidone (3 days) Clinical Global serious adverse events. The transition from IM to
transitioned to oral Impression (CGI); oral ziprasidone was well tolerated.
ziprasidone (days 4 EPS
and 5)

Oosthuizen et South Prospective 35 patients with a first haloperidol for 12- PANSS; EPS Mean reduction in PANSS was 30.3% (SD
al. 2001 Africa Cohort episode of psychosis weeks 20.9%) at 6 weeks and 41.4% (SD 16.6%) at 12
weeks. No significant changes in mean
extrapyramidal symptoms.

J Clin Psychopharmacol. Author manuscript; available in PMC 2021 February 11.

M. R. Olivier South Prospective 92 patients with first 100 healthy flupenthixol PANSS; Significant group × time effect (p ≤ 0.0001) for
et al. 2015 Africa Case Control episode schizophrenia controls decanoate for 12 MATRICS Cognitive the MCCB composite score. For other MCCB
months Consensus Battery domains there were significant group × time
(MCCB) composite effects for attention and vigilance (p ≤ 0.0001),
score over 12 months visual learning (p ≤ 0.0001), verbal learning (p =
0.005) and working memory (p ≤ 0.0001).
Moderate correlations between change in MCCB
composite score and change in symptomatology.

Kaminga et al. Malawi Prospective 126 first episode antipsychotic for 18 Remission in positive 98 (78%) completed follow-up, 70 (71.4%)
2018 Cohort psychosis patients (aged months and negative symptoms remitted within mean duration of 8.05 (4.54)
18-65) defined by the Remission months. Long DUP, poor insight, being
in Schizophrenia separated/divorced/widowed, deteriorating
Working Group criteria premorbid functioning, family history of
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Author/Year Country Study Design Sample Description Control Treatment Outcome Measurement Results
psychiatric disorders, and male gender delayed
remission.

Saloojee et al. South Prospective 67 antipsychotic naive 67 controls antipsychotic for 12 Side Effects: Metabolic Of 64 study subjects without baseline metabolic
2017 Africa Cohort patients with a first months Syndrome measured syndrome, only 36 completed the 12-month
Kumar et al.

episode of severe mental using the 2009 Joint follow-up (response rate 56.3%). The incidence
illness Interim Statement of metabolic syndrome was 5.5%.
criteria (Albert et al.
2009)

B. Chiliza et South Prospective 107 largely antipsychotic flupenthixol Side Effects: metabolic Significant increases in BMI (P < .0001), waist
al. 2015 Africa Cohort naïve, first-episode decanoate for 12 syndrome, body mass, circumference (P = 0.0006) and triglycerides (P
schizophrenia patients months fasting blood glucose and = 0.03) and decrease in HDL (P = 0.005).
lipids Change in BMI was only correlated with change
in triglycerides (P = .008). Only significant
predictor of BMI increase was lack of substance
abuse (P = .002).

Emsley et al. South Prospective 22 never-treated, non- 23 healthy risperidone or Side effects: brain Caudate but not putamen sizes were larger in
2015 Africa Cohort substance-abusing controls flupenthixol long volume changes on MRI, patients at baseline. No significant group x time
patients with first-episode acting injection psychopathology, insight, interactions were found for any MRI regions.
schizophrenia or functionality, cognitive
schizophreniform performance, and motor
disorder symptoms

Emsley et al. South Prospective 23 previously 53 matched lowest possible dose Side effects: brain Excessive cortical volume reductions were
2017 Africa Cohort antipsychotic naive healthy of flupenthixol volume changes, EPS, observed in patients, with no significant group
patients with a first individuals decanoate depot weight gain differences for changes in subcortical grey matter
episode of schizophrenia formulation and white matter volumes. In multiple regression
or schizophreniform model, the only significant predictor of cortical
disorder volume change was total antipsychotic dose
received (p= 0.04). No significant association
between cortical volume changes and
psychopathology, functionality, and
extrapyramidal symptoms or age, gender, and
duration of untreated psychosis.

Emsley et al. South Prospective 22 antipsychotic naive 23 healthy risperidone long Brain volume on MRI Ventral diencephalon volume reduction
2015 Africa Cohort patients with first episode volunteers acting injection or correlated bilaterally with body mass increase
schizophrenia flupenthixol and HDL-cholesterol reductions, and unilaterally
decanoate for 13 with blood glucose elevation.
weeks

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Emsley et al. South Prospective 45 clinically stable quetiapine and Side Effects: change in No between-group differences for BMI (F=1.90,
2005 Africa Randomized patients with haloperidol for 52 BMI and glycosylated p=0.1) and HBA1c (F=1.17, p=0.3) values, and
Parallel Group schizophrenia weeks haemoglobin (HBA1c) there were no significant changes in BMI for
Study levels either group. HBA1c levels decreased for the
haloperidol group (−1.5%, p=0.04), but not for
the quetiapine group (−0.3%, p=0.5).

Oosthuizen et South Prospective 40 subjects with first- 2 vs. 8 mg/d of Psychiatric Symptoms: Both treatments were equally effective in
al. 2004 Africa Randomized episode psychosis haloperidol for 6 PANSS; Side Effects: reducing the PANSS. Low dose haloperidol was
Controlled weeks extrapyramidal side better tolerated, with fewer extrapyramidal
Study effects effects, less frequent use of anticholinergic
medication and smaller prolactin elevations.
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Author/Year Country Study Design Sample Description Control Treatment Outcome Measurement Results
Landmark et South Prospective 93 South African Xhosa fluphenazine Length of hospital stay The combined treatment significantly shortened
al. 1994 Africa Randomized patients with decanoate depot the length of hospital stay. The combined
Controlled schizophrenia injection used alone treatment group also obtained significantly
Study or fluphenazine higher symptom improvement.
decanoate with
Kumar et al.

fluphenazine HCl IM

Emsley et al. South Prospective 45 patients aged 18 to 65 quetiapine (N = 22) Side effects: changes in The quetiapine group showed significantly
2004 Africa Randomized w/ tardive dyskinesia or Haloperidol tardive dyskinesia greater improvements in dyskinesia (6 and 9
(Active) with either schizophrenia (N=23) for 12 months [p ≤ .01]) and CGI dyskinesia. Response
Controlled or schizoaffective months rate (≥ 50% symptom reduction) was greater
Study disorder with quetiapine than haloperidol (64% [9/14] and
37% [6/16] at 6 months; 55% [6/11] and 28%
[4/14] at 12 months). Serum prolactin differed
significantly between groups (p=.005), with
elevation for haloperidol.

S. Brook et. al. South Prospective 44 patients age 18 - 65 parenteral Psych Symptoms: Brief No significant differences between the two
1998 Africa Randomized with schizophrenia, zuclopenthixol Psychiatric Rating Scale agents in efficacy and tolerability.
(Active) schizophreniform acetate (N=24) or (BPRS), Clinical Global
Controlled disorder and substance haloperidol (N=20) Improvement Scale
Study induced psychotic parenterally than (CGI) and the Simpson
disorder who required orally for 28 days Angus Scale (SAS)
acute neuroleptic
treatment

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