The prevalence of substance use disorder (SUD) in psychiatric disorders is high and has a detrimental impact on the course of illness
Around 40-60% of schizophrenia patients have a comorbid SUD, excluding tobacco5
Around 30% of patients with bipolar disorder have concurrent SUD in community-, and 40% in clinical settings.6,7
Those with comorbid SUD have a higher mortality ratio compared to those without SUD, regardless of gender or psychiatric disorder (schizophrenia, bipolar disorder, unipolar depression).8
Detrimental impact of SUD on bipolar disorder include worse adherence, earlier age of onset, worse treatment-response, more frequent relapses, more impaired psychosocial functioning, increased suicide risk.9
Continued cannabis-use in first-episode psychosis (FEP) leads to worse prognosis
High-frequency users of high-potency cannabis have an increased risk for relapse1
Continued cannabis use is also related to more relapses throughout the illness-course with shorter remission periods between relapses1
Continued cannabis use affects medication adherence negatively2
Reducing substance use is an important target of intervention in this patient group3
Dopamine plays a crucial role in addiction
Drug abusers have reduced number of dopamine D2 receptors and dopamine release, as indicated by PET studies4
Deficient dopamine activity has been associated with loss of control and compulsive drug consumption4
Reductions in dopamine function negative impairs sensitivity to natural reinforcers, like food or water. 4
Restoring brain dopaminergic tone and the activity of cortical projection could be a target of therapeutic interventions4
Dopamine D3 receptors could be a target of intervention for patients with dual diagnosis
D3 receptors are preferentially located in mesolimbic regions and the prefrontal cortex โ areas that mediate aspects of addiction, like reward, emotion, motivation, drug seeking,ย and relapse10
D3 receptors have the highest affinity to dopamine, therefore they are the most sensitive to elevations in dopamine levels during substance use10
Repeated consumption of substances result in an upregulation of D3 receptor expression (sensitisation)10; PET studies have shown increased levels of D3 receptors in the ventral pallidum, substantia nigra and the globus pallidus in methamphetamine and cocaine abusers11
Cariprazine, a D3-preferring dopamine D2-D3 partial agonists, is a promising treatment option for dual diagnosis patients, as supported by real-world evidence
Among antipsychotics, cariprazine has the highest affinity to D3 receptors โ higher than that of dopamine itself, making it the only antipsychotic that can occupy the D3 receptors in the presence of dopamine in the human brain12
Cariprazine effectively reduced methamphetamine craving and use, as well as yielded global functional improvement in patients with comorbid methamphetamine use disorder and psychosis13
A patient with persistent methamphetamine-induced psychosis and negative symptoms experienced an reduction in substance craving and use as well as improvement in psychotic and negative symptoms14
Another case series described two patients with schizophrenia and concurrent substance use disorder where cariprazine improved positive and negative symptoms while maintaining abstinence15
A patient with schizophrenia, substance abuse and cognitive dysfunction experienced marked improvements in all domains and became abstinent with cariprazine treatment16
References
- Schoeler, T. et al. Effects of continuation, frequency, and type of cannabis use on relapse in the first 2 years after onset of psychosis: an observational study. The Lancet Psychiatry 3, 947โ953 (2016).
- Schoeler, T. et al. Poor medication adherence and risk of relapse associated with continued cannabis use in patients with first-episode psychosis: a prospective analysis. The Lancet Psychiatry 4, 627โ633 (2017).
- Schoeler, T. et al. Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. The Lancet Psychiatry 3, 215โ225 (2016).
- Volkow, N. D., Fowler, J. S., Wang, G. J., Baler, R. & Telang, F. Imaging dopamineโs role in drug abuse and addiction. Neuropharmacology 56, 3โ8 (2009).
- Compton, W. M., Thomas, Y. F., Stinson, Frederick, S. & Grant, B. F. Prevalence, Correlates, Disability, and Comorbidity of DSM-IV Drug Abuse and Dependence in the United States. Arch. Gen. Psychiatry 64, 566โ576 (2007).
- Hunt, G. E., Malhi, G. S., Cleary, M., Lai, H. M. X. & Sitharthan, T. Prevalence of comorbid bipolar and substance use disorders in clinical settings, 1990โ2015: Systematic review and meta-analysis. J. Affect. Disord. 206, 331โ349 (2016).
- Hunt, G. E., Malhi, G. S., Cleary, M., Lai, H. M. X. & Sitharthan, T. Comorbidity of bipolar and substance use disorders in national surveys of general populations, 1990โ2015: Systematic review and meta-analysis. J. Affect. Disord. 206, 321โ330 (2016).
- Hjorthรธj, C. et al. Association between alcohol and substance use disorders and all-cause and cause-specifi c mortality in schizophrenia, bipolar disorder, and unipolar depression: a nationwide, prospective, register-based study. Lancet Psychiatry 2, 801โ808 (2015).
- Preuss, U. W., Schaefer, M., Born, C. & Grunze, H. Bipolar Disorder and Comorbid Use of Illicit Substances. Medicina (B. Aires). 57, 1256 (2021).
- Sokoloff, P. & Le Foll, B. The dopamine D3 receptor, a quarter century later. Eur. J. Neurosci. 45, 2โ19 (2017).
- Boileau, I. et al. Higher binding of the dopamine D3 receptor-preferring ligand [11C]-(+)-propyl-hexahydro-naphtho-oxazin in methamphetamine polydrug users: A positron emission tomography study. J. Neurosci. 32, 1353โ1359 (2012).
- Stahl, S. M. Mechanism of action of cariprazine. CNS Spectr. 21, 123โ127 (2016).
- Truong, T. T. & Li, B. Case series: Cariprazine for treatment of methamphetamine use disorder. Am. J. Addict. 31, 85โ88 (2022).
- Ricci, V., Di Salvo, G. & Maina, G. Remission of persistent methamphetamine-induced psychosis after cariprazine therapy: presentation of a case report. J. Addict. Dis. 0, 1โ4 (2021).
- Carmassi, C. et al. Clinical Experiences with Cariprazine in Schizophrenic Patients with Comorbid Substance Abuse. Evid. based Psyxhiatric Care 05, 11โ14 (2019).
- Rodriguez Cruz, J., Sahlsten Schรถlin, J. & Hjorth, S. Case Report: Cariprazine in a Patient With Schizophrenia, Substance Abuse, and Cognitive Dysfunction. Front. Psychiatry (2021) doi:10.3389/fpsyt.2021.727666.
