Double trouble - managing comorbidity in schizophrenia

For healthcare workers, overcoming comorbidities in psychotic disorders is rarely straightforward as it is closer to the norm rather than the exception. Here we review some interesting developments in managing dual diagnoses.

All too frequently, patients with schizophrenia co-present with a substance use disorder, including alcohol use disorder, that leads to or is associated with the exacerbation or alteration of their mental health condition. 


Smoking and schizophrenia

Smoking is common among those with schizophrenia. Thus, while the prevalence of smoking in the total U.S. population is about 14%, the prevalence among people with schizophrenia is considerably higher – between 70% and 85%.1,2

The prevalence of smoking in the U.S. population is about 14 percent; among people with schizophrenia it’s 70-85%

Given the known serious health consequences of smoking, finding ways to help those with schizophrenia to stop is important. However, the neurochemistry underlying their addiction may be different in those with schizophrenia than in the general public.

Considerable research is underway to determine the central mechanisms underlying this heavy dependence on nicotine and to devise therapies and strategies specifically to help those with schizophrenia quit smoking successfully.


Cannabis in schizophrenia – a causal relationship?

It is known that those with first episode psychosis (FEP) or schizophrenia are more likely than members of the general population to use or to have used cannabis.3 Also known is that cannabis use does not occur in isolation – it’s linked to a wide range of confounding variables.3

However, what is unknown is whether cannabis causes psychosis. But can such a relationship ever be proven?

One way would be to compare cannabis use and non-use in naïve youngsters in a RCT to see how many of them become psychotic. Clearly, such an approach is not feasible due to the large numbers of subjects needed. Nor would it be ethical!3


Proving the impossible

Given the level of confounding variables, the authors of a large literature study conducted in 2016 concluded that trying to focus “exclusively on the cannabis-psychosis association will be of little value in our quest to better understand psychosis and how and why it occurs”.3

Psychiatric disorders and cognitive impairments are consistently associated

A more recent combined assessment of systematic reviews, meta-analyses and other literature of heavy and dependent cannabis use is slightly more up-beat. While not proving causality, the review showed a consistent association of use of cannabis with psychiatric disorders and cognitive impairments that recovers after a period of abstinence.4


Civil obedience

More recently still, the findings of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III) have been reported.5 This is a survey of the civilian noninstitutionalized US population and included 36,309 respondents. Of these, 11,755 were aged 18-34 of whom 264 had a diagnosis of schizophrenia/psychosis.

To study factors around new onset of schizophrenia, all diagnosed respondents undertook the Alcohol Use Disorder and Associated Interview Schedule (AUDADIS-5). This was to determine likely involvement of underlying variables, such as use of cannabis, nicotine and other drugs in their diagnosis.


The importance of confounding factors

Early adolescent use of cannabis was significantly associated with schizophrenia. However, once the analysis was adjusted for covariates, the statistical significance disappeared. The authors conclude that their study highlights the importance of confounding factors when examining the relationship between cannabis use early in adolescence and schizophrenia and psychosis.


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Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


  1. Creamer MR, et al. Morb Mort Weekly Report 2019;68:1013-1019
  2. Ziedonis D, et al. Nicotine Tob Res 2008;10:1691-1715
  3. Ksir C, Hart CL. Curr Psychiatry Rep 2016;18:12 DOI 10.1007/s11920-015-0657-y 
  4. Kroon E, et al. Addiction 2019;115:559-572
  5. Ryan J, et al. Schizophr Res 2020;215:482-484


Further reading

Winklbaur B, et al. Dialogues Clin Neurosci 2006;8:37-43