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The Link Between Psychotic Disorders and Substance Use

The Link Between Psychotic Disorders and Substance Use

Psychotic disorders are a group of syndromes characterized by positive symptoms, including hallucinations, delusions, and thought disorder; and negative symptoms, including mood symptoms, social withdrawal, and reduced motivation. Cognitive deficits also appear with psychotic disorders. Psychotic disorders rank 22nd in the World Health Organization's list of worldwide causes of disability.1 This ranking is adjusted for the relatively low lifetime prevalence rate for psychosis; the perceived burden of the disease on those affected with psychotic disorders, as well as their relatives and caregivers, is much higher.2 Some symptoms are present, albeit in an attenuated form, prior to the onset of a diagnosable disorder. Features of psychotic disorders are detectable in the general population and are referred to as schizotypal traits, representing a normally distributed trait of risk for psychosis.

A recent large study of patients in their first episode of psychosis found a 74% lifetime prevalence of a substance use disorder, with 62% of the sample presenting at baseline with current substance use.3 Alcohol, nicotine, and cannabis are the predominant substances abused by patients with psychotic disorders.4 A US epidemiology study reported the risk for substance use as 4.6 fold higher in patients with schizophrenia compared with the general population.5 Even in Sweden, where there are tight restrictions on the sale of alcohol, patient consumption far exceeds rates reported in the general population.6

Relationship with onset
There has been much discussion about the relationship between recreational drug use, psychotic symptoms, and psychotic disorders, particularly with the increasing tolerance for drugs such as cannabis (by society and government). Substance use patterns seem to establish themselves before the onset of psychotic disorders; in a significant proportion of individuals, this may be as little as a month before the first signs of illness.7 The close temporal proximity of substance use to emerging signs or symptoms of psychotic illness may be an indication for the causal relationship between psychotic disorders and substance use, although this is open for
debate.8

It is difficult to determine whether those prone to psychosis are self-medicating initial symptoms, or whether they are drawn to substance use by factors unrelated to illness, such as personality traits. In addition, patterns of substance use before onset of illness may be indicative of other risk factors that are associated with lifestyle changes linked to the beginning of deterioration into psychosis and detrimental factors directly related to increased drug use.

There are 2 hypotheses regarding the onset of psychotic disorders that are of interest to researchers and clinicians:

  • Drug use triggers psychotic symptoms in those individuals who have an underlying predisposition to psychotic disorders.
  • Exposure to recreational drug use is sufficient in itself to lead to these symptoms independent of underlying predisposition.

The NEMESIS project tested these hypotheses in regards to cannabis use. Van Os and colleagues9 reported that those who displayed a vulnerability to psychotic disorders at baseline were more likely to experience isolated psychotic symptoms after cannabis use. In addition, use of cannabis alone led to
the increased likelihood of isolated psychotic symptoms reported at follow-up. Furthermore, one study found higher
reports of psychotic-like and psychopathologic experiences from cannabis use (both during the immediate high and during following use) in those individuals with an elevated propensity toward psychosis.10 These data suggest that cannabis use may trigger an underlying vulnerability to isolated symptoms through an unknown mechanism. There is limited evidence that perhaps in high doses,11 cannabis in the absence of any vulnerability can lead to isolated psychotic symptoms. However, isolated incidences of psychotic symptoms are not sufficient for a diagnosis of any psychotic disorder, and therefore, there are additional factors that lead to the onset of a psychotic disorder.

The most robust body of evidence for the relationship between the onset of psychotic disorders and drug use comes from the Swedish conscript studies.12,13 Baseline drug use information was taken at intake to the army for these studies. The authors found that cannabis use, and to a lesser extent amphetamine use, predicted onset of psychotic disorder later in adulthood. The explanatory variable was age at use, with younger age predicting psychotic disorders. This relationship did not exist for other drugs used, such as cocaine. A more recent cohort study in New Zealand confirmed the relationship between cannabis use and the onset of psychotic disorders.14 This study demonstrated that younger age of first cannabis use predicted younger age of psychotic disorder onset in individuals with the Val/Val genotype for COMT on the Val158Met polymorphism (a gene that codes for the activity level of an enzyme involved in the breakdown of dopamine).

Course of psychosis and
substance use
There is conflicting evidence of the effects of substance use on age at psychotic disorder onset. Some studies have found that substance use leads to a younger age at symptom onset and/or diagnosis,7,15,16 while other studies have found no association.17 Some investigators have suggested that patients who have an onset related to drug use have a distinct subtype of psychotic disorder. Drug-induced psychosis is still considered diagnostically distinct from psychotic disorders, since in the former, symptoms abate when substance use is discontinued, while symptoms in the latter persist. However, as previously noted, those who experience isolated psychotic symptoms in relation to drug use may have an underlying predisposition to psychosis.

Substance use during the course of psychotic illness may have implications for relapse and may interfere with treatment. Thus, finding predictors of continued use following an initial psychotic episode would identify those patients who may require further interventions and/or close monitoring. The most
consistently reported predictors of continued use are young age and male sex.15,16,18 Previous studies have reported that young men are significantly more likely to use substances or to use more than one substance; this helps explain why male sex proves to be a significant
predictor of continued use.6 Compared with patients who have just substance use disorder, patients with psychotic disorder and substance dependence are more likely to be using substances after 7 years.19 This further suggests that those with more severe substance use problems should be identified for targeted interventions concerned with reducing substance use.

However, there is some suggestion that substance use decreases following treatment initiation. Three studies have examined the course of substance use in the early phases of psychotic disorders. Two have shown a marked reduction in substance use during early treatment, compared with that in the pretreatment period.18,20 A third study found that 1 in 5 patients with psychotic disorders stopped using substances 15 months after their first episode.21 Those patients who continued use did not increase their baseline use, and very few patients developed substance use behavior after treatment began. Taken together, these studies offer some room for optimism. It seems that a significant proportion of patients with psychotic disorders decrease or discontinue substance use once treatment has been initiated, while those who continue use do not increase their intake.

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