Cannabis disorders and readmission

We found univariate associations between baseline cannabis and outcome; however these were no longer significant after controlling for age, gender and diagnostic subtype. Our findings are consistent with studies reporting that baseline cannabis use did not predict poor outcome. ^{Reference Gonzalez-Pinto, Alberich, Barbeito, Gutierrez, Vega and Ibanez2,Reference Addington and Addington18} Some of the apparent association between baseline cannabis use and adverse outcome may be due to confounding of cannabis disorders with other factors which predict readmission, namely, being younger, male and having a primary diagnosis of schizophrenia. Baseline use of cannabis or other drugs may also be a predictor of ongoing drug use.

Stimulant disorders and readmission

Stimulant disorders at baseline were not associated with readmission, but hospital admissions with stimulant disorders prior to the index admission were. The finding is consistent with evidence that the risk of developing drug-related psychosis after prolonged drug use is greater for stimulants than for cannabis, ^{Reference Degenhardt, Roxburgh and McKetin19} and with sensitisation models of the interaction between stimulant use and psychosis. ^{Reference Curran, Byrappa and Mcbride20,Reference Hermens, Lubman, Ward, Naismith and Hickie21} Prior stimulant-related admissions are likely to be indicators of severe or enduring stimulant use, since most people with stimulant misuse or dependence are not admitted to hospital. Severe stimulant disorders may also be associated with misuse of a wider range of substances, including heavier or more sustained cannabis use. However, the same association was not found for prior cannabis use disorders.

Fig. 2 Readmission within 2 years of first admission for psychosis, by pattern of ongoing problem drug use.

Results for 4993 persons (69% of total sample) for whom a proxy measure of ongoing drug problems was available. Two-year readmission rate for total sample: 37%.

Ongoing drug use

We found that people with ongoing problem drug use had a rate of readmission nearly a third higher than people with no drug use. An association between ongoing drug use and poor outcome is not surprising, however our findings help to quantify the scale of this effect in a representative population-based sample, and underline the significant personal and health system impacts of ongoing drug use.

Conversely, we found that the best outcome (as measured by hospital readmission) occurred in people with baseline substance diagnoses but no ongoing substance use problems. Several studies have found that young people with psychosis who cease substance use have better outcomes than those who have never used substances. ^{Reference Strakowski, DelBello, Fleck, Adler, Anthenelli and Keck22-Reference Lambert, Conus, Lubman, Wade, Yuen and Moritz24} A recent meta-analysis of this issue concluded that further and larger studies were needed. ^{Reference Gupta, Mullin, Nielssen, Harris and Large25} Our findings add further evidence on this issue.

An association between substance use and positive outcome in psychosis may seem counterintuitive, since substance use in people with psychosis is associated with negative prognostic factors including younger age, male gender and social disadvantage. However, there is increasing evidence that comorbid drug use in psychosis is also associated with better neurocognitive performance, fewer negative symptoms, fewer neurological soft signs and more positive symptoms. ^{Reference Rabin, Zakzanis and George26,Reference Yucel, Bora, Lubman, Solowij, Brewer and Cotton27}

Three explanations have been proposed for these findings. First, cannabis may have direct neuroprotective effects. ^{Reference Yucel, Bora, Lubman, Solowij, Brewer and Cotton27} Second, Meuser et al ^{Reference Mueser, Drake and Wallach28} have proposed that this effect is mediated through social competence, whereby more ‘socially oriented patients with serious mental illness are more likely to come into contact with drugs and subsequently develop substance use disorder’ (p. 726). Third, these findings may reflect varying degrees of personal vulnerability: psychosis in the absence of substance use is likely to reflect greater genetic or developmental diathesis in the person affected, whereas cannabis or other drugs may precipitate psychosis in individuals with less intrinsic vulnerability. ^{Reference Schnell, Koethe, Daumann and Gouzoulis-Mayfrank29,Reference Loberg and Hugdahl30} Our findings cannot distinguish between greater social competence and lesser personal vulnerability as explanations for positive outcome in former drug users with psychosis, and further research on this question is needed. The association between ongoing substance use and worse outcome is inconsistent with cannabis having a neuroprotective effect in psychosis.

Regardless of the mechanism, our findings underline an important and hopeful clinical message. Young people with first-episode psychosis and comorbid substance disorder may have the best outcomes, provided that substance disorder is properly managed.

Other findings

After controlling for other variables, the risk of readmission for people with an index diagnosis of drug-induced psychosis was higher than for those with an index diagnosis of schizophrenia. This is consistent with studies questioning the predictive validity of drug-induced psychosis diagnoses. ^{Reference Mathias, Lubman and Hides31,Reference Crebbin, Mitford, Paxton and Turkington32} In a study of persons with diagnoses of cannabis-induced psychosis, nearly half were subsequently diagnosed with schizophrenia and 77% had further psychotic episodes. ^{Reference Arendt, Rosenberg, Foldager, Perto and Munk-J⊘rgensen33}

The association between ongoing problem drug use and readmission was not constant over time; cessation of problem drug use appeared to be associated with a reduced risk of early readmission (within 90 days of discharge from index admission). Early and late relapse or readmission may be influenced by different processes and risk factors. ^{Reference Durbin, Lin, Layne and Teed34} This issue warrants further study.

Limitations

The scale and population coverage of administrative data-sets can complement clinical studies by allowing an examination of issues such as stimulant misuse which may be otherwise confounded by other clinical or personal variables in smaller clinical samples. However, routinely collected administrative data also have a number of limitations.

First, we have not captured all incident cases of psychosis in NSW because we have used hospitalisation data to define incidence. More than 80% of people seen by specialised early psychosis services are admitted early in their illness. ^{Reference Sipos, Harrison, Gunnell, Amin and Singh35-Reference Wade, Harrigan, Harris, Edwards and McGorry37} Those not admitted have longer duration of psychosis, less social disadvantage and greater likelihood of manic psychosis, ^{Reference Sipos, Harrison, Gunnell, Amin and Singh35,Reference Wade, Harrigan, Harris, Edwards and McGorry37,Reference Compton, Gordon, Goulding, Esterberg, Carter and Leiner38} but do not differ in their prevalence of positive symptoms or the likelihood of problem substance use. ^{Reference Wade, Harrigan, Harris, Edwards and McGorry37} Our findings underestimate the total number of young people with psychosis, and our sample omitted some young people with better social support and/or a less acute onset.

Second, we do not have follow-up information on all study participants. Thirty-one per cent of participants had neither a readmission to hospital nor a contact with NSW community mental health services during the follow-up period. These individuals were younger, more likely to have index diagnoses of brief, atypical and drug-induced psychoses and to have prior (but not baseline) cannabis and stimulant diagnoses. In the Australian health system, state-operated mental health services care for most persons with psychosis. Loss of contact with specialised services may be a sign of resolution of symptoms and recovery from illness. ^{Reference Warner39,Reference Emsley, Chiliza, Asmal and Lehloenya40} However, people losing contact with specialised services may have equivalent rates of positive symptoms and substance use to those remaining in care. ^{Reference Stowkowy, Addington, Liu, Hollowell and Addington41} We cannot know whether those with no follow-up may have had ongoing substance use or psychosis for which they did not seek care, or were managed without contact with NSW in-patient or community mental health services.

Third, we used hospital readmission as a measure of relapse. Lack of readmission does not equate with symptomatic or functional recovery, and many significant relapses of psychoses may be managed without readmission. We did not have a measure of the severity of psychotic symptoms or of substance use. However, hospital readmission remains the most widely used indicator of relapse in young people with psychosis, ^{Reference Gleeson, Alvarez-Jimenez, Cotton, Parker and Hetrick9} and a second hospital admission may be a very significant event for a young person and for their family.

Fourth, we have examined admissions prior to the index psychosis admission with stimulant or cannabis diagnoses. Most people with substance use disorders (misuse or dependence) are not admitted to hospital with those disorders. Therefore this measure of prior substance disorder is likely to be of high specificity but low sensitivity.

Finally, our proxy measure of ongoing drug use was imprecise. It combined data from in-patient and community diagnoses with a clinician rating of problem substance use derived from the HoNOS. The HoNOS is not a diagnostic instrument and does not distinguish the type of drug used.

Clinical implications

Cannabis or stimulant disorders at first hospital admission with psychosis may not be negative prognostic signs. Young people with substance comorbidities may have both the best and worst of outcomes, depending on whether problematic substance use is discontinued. It is critical to screen and offer intervention for drug use in early psychoses. Admissions with stimulant disorder diagnoses prior to the first psychosis admission were associated with worse outcome. This suggests that it is important not only to identify current substance use at first admission with psychosis but also to obtain a detailed history of the type, severity and duration of past substance use.