Treatment of substance use disorders in schizophrenia: A unifying neurobiological mechanism?

Abstract

Substance use disorders (SUDs) are highly prevalent and are associated with poor outcomes among individuals with schizophrenia. Integrating treatments for both disorders improves outcomes. Numerous individual pharmacologic and psychosocial treatments have shown effectiveness at reducing substance use in individuals with a primary diagnosis of schizophrenia and co-occurring substance use disorders. Of these treatments, medications such as certain atypical antipsychotics and naltrexone, and psychosocial treatments such as contingency management, seem to be particularly promising. The development and evaluation of psychopharmacologic and psychosocial treatments for SUDs in schizophrenia would benefit from a better understanding of the neurobiological mechanisms underlying the effectiveness of such treatments. Several theories have been put forth to explain the heightened risk for SUDs in schizophrenia. Of these, brain reward circuitry dysfunction, hypothesized to be etiologically important in SUDs, may be an especially salient target for treatments aimed at the reduction of substance use in patients with schizophrenia. We review current pharmacologic and psychosocial treatments for SUDs in schizophrenia, and theoretical mechanisms underlying the increased risk for SUDs in this population. We propose that effective treatments may in part work through the modulation of brain reward circuitry dysfunction.

Substance abuse and schizophrenia: Pharmacotherapeutic intervention

“…5.1 A possible neurobiological basis for the effects of clozapine in patients with schizophrenia and co-occurring substance use disorder As noted above, several authors (Green, Zimmet, Strous, & Schildkraut, 1999;Chambers, Krystal, & Self, 2001;Roth, Brunette, & Green, 2005) have proposed that a brain reward circuit dysfunction may underlie substance use disorders in patients with schizophrenia. The reward deficiency formulation of the basis of substance use in patients with schizophrenia proposes that people with schizophrenia have a dysfunction in their dopamine-mediated brain reward pathways in the mesocorticolimbic tracts, which underlies their alcohol and substance use.…”

“…Whether quetiapine, which produces a relatively weak D2 blockade, or aripiprazole, which is a partial dopamine agonist (Kane et al, 2002), will decrease substance abuse in these patients as clozapine seems to do remains to be determined. Moreover, how the apparent effect of naltrexone (a medication that, in essence, blocks reward circuitry in the brain) relates to this neurobiological formulation is not clear at this time (Roth, Brunette, & Green, 2005).…”

“…Green and colleagues (Green, Zimmet, Strous, & Schildkraut, 1999;Roth, Brunette, & Green, 2005) and others (Chambers, Krystal, & Self, 2001) have proposed an alternative, neurobiological hypothesis. This formulation, based on a series of animal studies (Svensson et al, 1995), suggests that the dysregulated dopamine-mediated mesocorticolimbic brain pathways that are thought to underlie the symptoms of schizophrenia are also the basis of a brain reward circuit deficit in these patients.…”

“…This formulation, based on a series of animal studies (Svensson et al, 1995), suggests that the dysregulated dopamine-mediated mesocorticolimbic brain pathways that are thought to underlie the symptoms of schizophrenia are also the basis of a brain reward circuit deficit in these patients. Green et al have further proposed that substances of abuse transiently lessen this deficit (and thus allow patients with schizophrenia to enjoy normal activities) while, unfortunately, they also worsen the course of schizophrenia (Green, Zimmet, Strous, & Schildkraut, 1999;Roth, Brunette, & Green, 2005). Studies are underway to confirm the existence of this brain reward circuit deficiency in patients with schizophrenia.…”

Substance Use Disorder Comorbidity in Schizophrenia

“…[65] Tipik antipsikotik ajanlar, şizofreni tanılı hastalarda alkol ve madde kullanımını azaltmamaktadır, çünkü beyindeki dopaminerjik mesokortikolimbik sinyal iletim kapasitesini arttırmayı başaramamaktadırlar. [66,67] Bunun yanı-sıra, güçlü D2 reseptör bloke etme özellikleri nedeniyle, ödül ile ilişkili uyaranlara yönelik yanıtların aksamasına neden olurlar. [66] 1990'dan itibaren şizofreni tanılı hastalarda atipik ajanların kullanımının başlanması ile alkol ve madde kullanım eş tanısı olan şizofreni tanılı hastalarda da bu grup ajanların daha faydalı olduğu izlenmiştir.…”