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\begin{document}

\title{A community pharmacist's intervention in antipsychotic drug-induced
sexual dysfunction in a patient with schizophrenia}



\author[1]{Masaki Maehara}%
\author[1]{Masayasu Sugiyama}%
\affil[1]{Sugiyama Pharmacy}%


\vspace{-1em}



  
  \date{June 14, 2024}


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\selectlanguage{english}
\begin{abstract}
Sexual dysfunction (SD) is a common side effect of antipsychotics. The
community pharmacist assessed a patient with SD and suggested a change
in prescription from risperidone and haloperidol to aripiprazole that
improved SD. This is the first report on amelioration of
antipsychotic-induced SD by early intervention by community pharmacists.%
\end{abstract}%



\sloppy


\textbf{Case report}

\textbf{A community pharmacist's intervention in antipsychotic
drug-induced sexual dysfunction in a patient with schizophrenia}

Masaki Maehara and Masayasu Sugiyama

Sugiyama Pharmacy, 525-2 Mitsusawa, Ogoori, Fukuoka, 838-0106 Japan

Email: mmaeharaph@yahoo.co.jp

Data availability statement: Data available on request due to
privacy/ethical restrictions

Funding statement: No funding

Conflict of interest disclosure: None

Ethics approval statement: None, because this is a case report.

Patient consent statement: Yes

Permission to reproduce material from other sources: We do not use any
reproduce material from other sources.

\textbf{Case report}

\textbf{A community pharmacist's intervention in antipsychotic
drug-induced sexual dysfunction in a patient with schizophrenia}

\textbf{Summary}

\textbf{What is known and objective:} Sexual dysfunction (SD) is a
common side effect of antipsychotics. We report a case of schizophrenia
wherein SD ameliorated after community pharmacist's intervention.

\textbf{Case summary:} A 60-year-old Japanese man with schizophrenia
stabilized after receiving risperidone, haloperidol, and antidiabetic
drugs. However, he complained of SD to a community pharmacist in our
pharmacy. The pharmacist interviewed his SD and suggested a change in
prescription from risperidone and haloperidol to aripiprazole that
improved his SD.

\textbf{What is new and Conclusion:} This is the first report on
amelioration of antipsychotic-induced SD by early intervention by
community pharmacists.

\textbf{Keywords:} Antipsychotic drugs, community pharmacy, sexual
dysfunction

\textbf{Key Clinical Message:} The community pharmacist interviewed a
patient with SD and suggested a change in prescription. Early
intervention by community pharmacists thereby helps ameliorate
antipsychotic drug-induced SD in a timely manner.

\textbf{WHAT IS KNOWN AND OBJECTIVE}

Sexual dysfunction (SD) is known to be a side effect of antipsychotic
drugs, and the prevalence of SD has been reported to be 30\%--80\% in
women and 45\%--80\% in men \textsuperscript{1}. A previous study has
shown that SD is worse in men than in women\textsuperscript{2}. There
are several types of symptoms of SD, including problems with sexual
arousal, penile erection, orgasms, and ejaculation \textsuperscript{2}.
SD was also reported to be one of the risk factors for decreased
medication compliance \textsuperscript{2}; in fact, 41\% of men
receiving antipsychotics stopped taking their medications due to SD
\textsuperscript{3}. Furthermore, SD is also related to poor
relationships with partners as well as negative effects on social and
personal life \textsuperscript{2}. Therefore, improvement of sexual
behaviour in patients may lead to a restored sense of well-being,
confidence, and dignity.

However, both patients and clinicians tend to avoid discussions
regarding sexual function, even though patients with treatment-resistant
schizophrenia have SD \textsuperscript{4}. In addition, clinicians are
likely to underestimate the prevalence of SD that is closely associated
with a patient's quality of life \textsuperscript{5}.Therefore, early
intervention by pharmacists may play an important role in the detection
and treatment of SD induced by antipsychotic drugs. Here, we report the
case of a 60-year-old man with schizophrenia whose SD was ameliorated
after intervention by a pharmacist in our community pharmacy.

DETAILS OF THE CASE

A 60-year-old Japanese man with schizophrenia stabilized after taking
risperidone (4.5 mg/day) and haloperidol (3 mg/day). He also received
anti-diabetic drugs such as metformin (750 mg/day), gliclazide (20
mg/day), and alogliptin (25 mg/day). One day, in our community pharmacy,
he complained to the community pharmacist about his SD, including
problems with erections, orgasm and satisfying orgasms. He was already
taking sildenafil, a drug to treat erectile dysfunction, but it had no
effect on his SD. Thus, the pharmacist interviewed his symptoms of SD.
He had the following problems: erection with difficulty, never reached
an orgasm and any satisfying orgasms. Therefore, the pharmacist
immediately reported these symptoms to his prescribing
doctor\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}and\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}recommended a reduction in the doses of risperidone and/or
haloperidol because these drugs may be responsible for the induction of
SD. Additionally, the pharmacist suggested switching from these drugs to
aripiprazole that may have fewer SD-related side effects among
antipsychotic drugs.

Following the pharmacist's suggestion, the doctor started prescribing 24
mg/day aripiprazole (Day 0) (Fig.1), while the doses of risperidone and
haloperidol did not change. As expected, his SD symptoms did not improve
14 days after the administration of aripiprazole. The dose of
risperidone was then reduced from 4.5 mg to 3 mg/day (Day 14). Three
weeks after a reduction in the dose of risperidone, his SD symptoms
still did not improve. Thus, the dose of haloperidol was reduced from 3
mg to 1.5 mg/day (Day 35). Three days after the reduction in the dose of
haloperidol, he engaged in sexual activity and acknowledged an improved
erection, orgasms and satisfying orgasms with somewhat difficulty (Day
38). Furthermore, 22 days after the reduction of haloperidol dose, his
SD symptoms had more alleviated in terms of erection, both reaching
orgasm and a satisfying orgasm and he did not feel any problems with
these symptoms (Day 57). However, he complained to the community
pharmacist about new symptoms such as ejaculatory dysfunction. Thus, the
pharmacist suggested to the doctor to further reduce the doses of
risperidone and/or haloperidol. The doctor decided to entirely stop the
use of haloperidol (Day 63), but his symptoms of ejaculatory dysfunction
did not improve 28 days after stopping the administration of haloperidol
(Day 91). Alternately, the dose of risperidone was tapered and
eventually withdrawn (Day 147). About three weeks after the withdrawal
of risperidone, his ejaculatory disorder substantially improved (Day
168). No alteration of his symptoms of schizophrenia and diabetes was
observed during the process of adding aripiprazole to haloperidol and
risperidone.

DISCUSSION

Previous studies reported that a patient's SD is associated not only
with side effects from the medication but also from several types of
diseases, such as psychiatric disease, diabetes, and cardiovascular
disease \textsuperscript{6}. Since the patient in the present case
suffered from both schizophrenia and diabetes, it is possible that these
diseases have contributed in part to the induction of SD. However, the
patient's SD improved upon switching from haloperidol and risperidone to
aripiprazole without any exacerbation of schizophrenia and diabetes,
indicating that his SD was caused mainly by haloperidol and/or
risperidone.

The mechanism of SD induced by antipsychotic drugs remains unclear, but
it is generally accepted that the blockade of monoaminergic receptors
such as dopamine may induce SD\textsuperscript{7}. For instance,
dopamine receptor blockade leads to decreased libido, erection, and
ejaculation, due to a dysfunctional reward and motivation system. In
addition, hyperprolactinemia due to dopamine receptor antagonism has
also been associated with the induction of sexual dysfunction
\textsuperscript{7} \textsuperscript{8}. In fact, both haloperidol and
risperidone, which induce hyperprolactinemia, have been shown to
increase the risk of SD as compared with other antipsychotic
drugs\textsuperscript{9}. In particular, 71.1\% of patients receiving
haloperidol over 12 months had SD\textsuperscript{10}. Furthermore,
67.8\% of patients taking risperidone for over one year also complained
regarding the symptoms of SD, such as reduced libido, erection
dysfunctions, and amenorrhea \textsuperscript{10}. On the other hand,
aripiprazole, which is classified as a prolactin-sparing drug, has been
reported to impart a lower risk of SD than other prolactin-sparing
antipsychotic drugs \textsuperscript{9}. As in the present report, a
previous study showed that switching from other antipsychotic drugs to
aripiprazole resulted in improved levels of prolactin and the
amelioration of SD without affecting efficacy \textsuperscript{11}.
These results suggest that prolactin levels are closely correlated with
the induction of SD.

The present report also showed that the ejaculatory dysfunction of
patients dramatically reduced after the withdrawal of risperidone.
Previous case reports indicated that risperidone caused ejaculatory
disorder, possibly through its adrenaline receptor
antagonism\textsuperscript{12} \textsuperscript{13}
\textsuperscript{14}. These results suggest that blockage of the
adrenaline receptor by antipsychotic drugs may be partially responsible
for the induction of ejaculation disorder.

There is no previous report showing a community pharmacist's
intervention in antipsychotic drug-induced SD in a patient with
schizophrenia. It is difficult for clinicians to assess all symptoms of
the patient's SD during medical examination. The present report showed
that the patient taking antipsychotic drugs complained of SD only to the
community pharmacist who interviewed the patient's symptoms of SD in
detail, reported them to the patient's prescribing doctor, and
recommended a change in prescription, resulting in dramatically
alleviated symptoms of SD. These results demonstrated the importance a
community pharmacist's intervention between the clinician and patient in
maintaining the appropriate medication and drug compliance in patients
receiving antipsychotic drugs.

WHAT IS NEW AND CONCLUSION

This is the first report of an appropriate intervention by a community
pharmacist to help ameliorate antipsychotic drug-induced SD in patients
with schizophrenia.

\textbf{Author contribution}

Masaki Maehara and Sugiyama Masayasu: We contributed equally to this
work.

\textbf{Funding statement}

We have no funding for this work.

\textbf{Conflict of interest disclosure}

We have no conflict of interests.

\textbf{Patient consent statement}

We obtained written informed consent from the patient for publication of
this case report.

\textbf{Acknowledgment}

None

\textbf{Ethical approval statement}

None

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3. Rosenberg KP, Bleiberg KL, Koscis J, Gross C. A survey of sexual side
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4. Kelly DL, Conley RR. Evaluating sexual function in patients with
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5. Dossenbach M, Hodge A, Anders M, et al. Prevalence of sexual
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11. Yoon HW, Lee JS, Park SJ, et al. Comparing the Effectiveness and
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12. Madhusoodanan S, Brenner R. Risperidone-induced ejaculatory and
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13. Holtmann M, Gerstner S, Schmidt MH. Risperidone-associated
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Psychopharmacol 2003;13:107-9.

14. Loh C, Leckband SG, Meyer JM, Turner E. Risperidone-induced
retrograde ejaculation: case report and review of the literature. Int
Clin Psychopharmacol 2004;19:111-2.

\textbf{List of Figure caption/legend}

Figure 1 Medication schedule in this case report

\textbf{Figure legend}

Patient was started on aripiprazole on day 0. The dose of risperidone
was reduced from 4.5mg to 3mg/day on day 14. The dose of haloperidol was
reduced from 3mg to 1.5mg on day 35. The dose of haloperidol and
risperidone was withdrawn on day 63, and day 147, respectively.\selectlanguage{english}
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