Cariprazine induced generalized edema – Case report
Authors: Dr. Aligandula Curie, Dr. Tanmayee Vuthandam, Dr. Ganta Akhila, Dr. Vijay Raj Pratheek. P, Dr. K. Ashok Reddy
Department of Psychiatry, SVS Medical College, Mahabubnagar.
INTRODUCTION
Schizophrenia is a chronic psychotic disorder
with varied presentation such as delusions,
hallucinations, disorganized behaviour,
disorganised speech, motor symptoms and
negative symptoms. Antipsychotics drugs are
first line treatment for schizophrenia. First
generation of typical antipsychotics even
though potent are more prone for Side effects
such as extrapyramimal symptoms, sedation,
hyperprolactinemia, etc. Second generation
antipsychotics thought to have lesser incidence
of side effects such as extra pyramidal
symptoms but can have symptoms of metabolic
syndrome and less effective in treating negative
and cognitive symptoms. Latest newer drugs
which are thought to be third generation such
as Aripiprazole, Brexiprazole, Cariprazine have
multiple effects targeting various symptom
domains of schizophrenia. These are found to
have lesser side effects also including both
extrapyramidal symptoms and metabolic
symptoms.
CARIPRAZINE
Cariprazine is a recently launched drug, which
is a novel anti psychotic for treating
schizophrenia. Hence there are lesser reported
side effects, still in monitoring
stage.Cariprazine is a dopamine receptor
partial agonist (DRPA) effective in the
treatment of negative symptoms of
schizophrenia with regard to self-care,
interpersonal relationships, and socially useful
activities. The pharmacological class of DRPAs
currently comprises three drugs (aripiprazole,
brexpiprazole, and cariprazine) among which
cariprazine displays the highest affinity to the
dopamine D3 receptor. Dopamine D3 receptors
are considered to play an important role in
mediating negative and cognitive symptoms of
schizophrenia. Cariprazine also binds to
dopamine D2 receptors with high affinity.
Cariprazine displays either agonistic or
antagonistic activity, depending on the
functional status of a neuronal system.
Cariprazine also binds to serotonin 5-
HT2B receptors with high affinity and to
serotonin 5-HT1A and 5-HT2A receptors with
moderate affinity. Review of case studies have
revealed that cariprazine is safe in wide range
of psychiatric disorders1. Studies on tolerability
and safety of cariprazine have reported lesser
side effects which included akathisia, insomnia,
parkinsonism and headache.2
MECHANISM OF ACTION
CASE REPORT
A middle aged married woman Mrs. M, on treatment
for schizophrenia since last 3-4 years presented
with delusion of persecution, reference, somatic
passivity, anhedonia, apathy and blunt affect after
stoppage of medication for last 2-3 months. Since
resperidone had been well tolerated in the past,
treatment with resperidone 8 mg/d was resumed.
On treating with resperidone 8mg, positive
symptoms had significantly improved but inspite of
multiple trials with other medication like amisulpiride
and aripiprazole negative symptoms persisted. She
was started on cariprazine 1.5mg initially and later While on Cariprazine
increased to 3mg with which her negative
symptoms subsided over 2-3 months and was
maintaining well.
On her regular follow-up 3 months after starting
Cariprazine, significant pitting type of pedal edema
on both lower limbs along with facial puffiness and
severe acne was noted which were present since 1
month. All the renal, liver and cardiac functioning
and other parameters were normal. Therefore,
cariprazine was reduced to 1.5 mg/d. 7 days after
reducing the dose of Cariprazine to 1.5 mg pedal
edema subsided completey, and facial puffiness
and acne reduced to some extent. Being a newer
molecule with very few documentations regarding
side effect profile, we suspected cariprazine to be 2 weeks after stopping Cariprazine
the culprit and stopped the medication with
Cariprazine and started on resperidone 8mg/day.
Facial puffiness and acne subsided within 2 weeks
of stoppage of Cariprazine.
DISCUSSION
To the best of our knowledge these have not previously been described as ADRs of
cariprazine in the literature, though there were case reports which reported parkinsonism,
akathisia in severe form and exacerbation of psychosis and hyperprolactinemia3,4.
Cariprazine being a newer molecule with very few documentations regarding side effect
profile. Our case reports on three suspected ADRs of cariprazine, namely facial puffiness,
pedal edema and acne.
As clinicians we need to be aware of unexpected side effects of newer drugs such as
Cariprazine for better and appropriate management. Further pharmacovigilance surveillance
is needed to assess their frequency.
Reporting newly recognized or unusually severe side-effects will help clinicians in daily
practice. We would like to share our observations within the field of psychiatry and beyond in
order to promote the timely detection ofADRs of cariprazine in the future, thus pursuing the
ultimate goal of improving patient safety.
REFERENCES
1.Csehi, R., Dombi, Z. B., Sebe, B., & Molnár, M. J. (2022). Real-Life Clinical Experience With
Cariprazine: A Systematic Review of Case Studies. Frontiers in psychiatry, 13, 82774. ………
https://doi.org/10.3389/fpsyt.2022.827744
2.Nasrallah, H. A., Earley, W., Cutler, A. J., Wang, Y., et al. (2017). The safety and tolerability of
cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis. BMC psychiatry,
17(1), 305. https://doi.org/10.1186/s12888-017-1459-z
3.Heck, J, Seifert, J, Stichtenoth, DO, et al. A case series of serious and unexpected adverse drug
reactions under treatment with cariprazine. Clin Case Rep. 2021; 9:e04084.
https://doi.org/10.1002/ccr3.4084
4.Pons-Cabrera, M. T., Palacios-Garrán, R., Tardón-Senabre, L., Fernández-Plaza, T, et al(2021).
Cariprazine-induced mania: A case series report. Bipolar disorders, 10.1111/bdi.13156. Advance
online publication. https://doi.org/10.1111/bdi.13156