Heroin and Schizophrenia: Subjective Responses to Abused Drugs in Dually Diagnosed Patients

Editors:

The prevalence of substance abuse among patients with mental disorders is high.¹ In particular, patients with diagnosed schizophrenia frequently report a history of abuse of cannabinoids and hallucinogenic drugs, often starting in the period preceding the onset of the psychosis.^{2, 3} According to clinical surveys, between 50% and 90% of patients with schizophrenia are regular cigarette smokers⁴ during the active (productive) phase of their disorder. Patients often report that smoking helps them to obtain relief from the unwanted effects of neuroleptic medications, such as sedation and drowsiness. Approximately 8% to 10% of patients with schizophrenia also abuse alcohol.^{5, 6} A lower number of patients use psychostimulants such as cocaine and amphetamines.^5-8 Even fewer patients with schizophrenia abuse opiates, because the level of social functioning necessary to carry out life as a heroin addict is often higher than that which a patient with schizophrenia is able to maintain.^{5, 7}

In a consecutive series of 135 patients addicted to heroin who were registered at the Alcohol and Drug Abuse Unit in Conegliano (Italy) from October 1997 to October 1998 for evaluation with a view to diagnosis and treatment, we found 5 patients (4 men, 1 woman) with a diagnosis of schizophrenia, which was made according to DSM-IV criteria on the basis of clinical history (including hospital admissions to psychiatric services) and a detailed interview to establish the presence of schizophrenic symptoms, whether "positive" (delusions; hallucinations; first-rank symptoms, so-called schneiderian experiences) or "negative" (apathy, avolition, anhedonia, affective flattening, autistic withdrawal).

The average age of the patients with psychosis was 31 years (range, 20-37), which was close to that of the total sample of addicts, whose average age was 30 years (range, 21-48). As for the nonpsychotic heroin addicts, for the 5 schizophrenic heroin addicts, the onset of substance abuse was during adolescence (age 13-17 years), generally marked by escalation from legal substances (alcohol and cigarettes) to cannabis and then to heroin (at approximately 18 years of age). In all but one patient, the onset of the psychotic symptoms coincided with the onset of illegal substance abuse and preceded the onset of long-term (10 years, on average) heroin abuse. In two of five patients, there was a family link for schizophrenia (mother and brother in one case; brother in the second case). Of the patients, the only female in the group lived alone, separated from her husband, in occasional employment; all male patients lived with their parents, had no stable affective relations, and were unemployed at the time of the study.

The symptom profile for all patients included "positive" symptoms (such as delusions, principally with persecutory themes; auditory hallucinations; in three cases, schneiderian experiences: telepathy and sensations of being influenced) and "negative" symptoms (apathy; anhedonia; social isolation, even to the point of autistic withdrawal) were also present. All patients but one were in contact with the psychiatric services: two were receiving neuroleptic treatment; two had previously had neuroleptic treatment, but with poor results; one had never taken antipsychotic medication.

Contrary to the behavior of the majority of heroin addicts in the sample, the schizophrenic patients ceased (or greatly limited) their use of cannabis and hallucinogenic drugs as a result of unwanted effects (including the worsening of psychotic symptoms). One patient admitted to alcohol and benzodiazepine abuse, both of which produced a "calming" effect on psychotic symptoms. All patients maintained occasional or frequent use of heroin for its euphorigenic effects. Heroin also seemed to significantly improve negative symptoms of the disorder (apathy, anhedonia, autistic withdrawal). The two patients who accepted long-term methadone treatment also reported an improvement in negative symptoms after receiving therapeutic dosages (50-80 mg/day) of the drug. In one case, higher methadone doses (100 mg/day) than usual seemed able to control the recrudescence of psychotic symptomatology during a sudden breakdown. Two schizophrenic patients also referred to the improvement of positive symptoms (ideas of reference, auditory hallucinations) after heroin use, an improvement which they also observed after neuroleptic treatment, but with a concurrent worsening of negative symptoms.

One cannot rule out that the secondary gain of obtaining acknowledgment for addictive behavior might have encouraged some of the five patients with schizophrenia to attribute greater therapeutic properties to heroin than those really experienced. The recognition of an impairing effect produced by cannabinoids and psychostimulants in these patients, however, contrasts with the persistent abuse observed in many other patients from the same series who tend to maintain the abuse of cannabinoids and other substances. It suggests that the five patients with schizophrenia studied were able to distinguish the effects of heroin and methadone on their symptomatology from the generic "high" effect obtainable with other substances.

It is hard to extrapolate more general indications from such a limited sample. This study is retrospective, is based on self-reported data, and does not have a formal control group. However, other studies have reported a positive effect of opioidergic agonists on psychotic symptomatology in patients with schizophrenia,^9-12 whereas preparations containing opioids, such as laudanum, have been used in the past with some success in the treatment of psychoses.¹³

We believe that the role of methadone as an antipsychotic drug needs to be studied further; a better under-standing of the actions of opiates in schizophrenia might lead to etiologic indications, the scope of which could well extend beyond the therapeutic usefulness of opiates for dually diagnosed patients. Heroin and related opioid substances, indeed, produce specific effects on the dopaminergic pathways that are believed to be involved in the pathogenesis of schizophrenic symptomatology.^{14, 15} In particular, opiates activate dopaminergic neurons in the mesolimbic circuits (accumbens).¹⁶ Such an increase in the activity of mesolimbic dopaminergic neurons is not associated with a concurrent increase in cortical dopaminergic neurons,^{17, 18} with frontocortical dopaminergic pathways apparently being less sensitive to the actions of opiates.¹⁸

We speculate that the improvement in negative symptoms reported by our five patients with schizophrenia after heroin use indicates a key role for a dopaminergic deficit in the mesolimbic area in the production of negative symptoms of schizophrenia. Mesolimbic and frontocortical dopaminergic pathways have specific and different roles in behavior control. Some studies indicate that dopamine activity in the prefrontal area may exert an inhibitory effect on subcortical dopaminergic functions.¹⁹ Recent studies on monkeys²⁰ have shown that hyperfunction of frontocortical dopamine projection is linked to a cognitive deficit of a type likely to be similar to that observed in patients with schizophrenia. Our observations (and those of others) of patients with schizophrenia^{10, 11} suggest that opioidergic agonists could partially correct an imbalance between hyperfunctioning frontocortical dopaminergic pathways (producing cognitive symptoms that include thought disorders) and hypofunctioning dopaminergic mesolimbic projections (producing part of the negative symptoms).

Paola Miotto, MD¹

Antonio Preti, MD²

Michela Frezza, PhD¹

¹Alcohol and Drug Abuse Unit; Conegliano, Italy

²Genneruxi Medical Center; I-09129 Cagliari, Italy