Substance use: a powerful predictor of relapse in schizophrenia

doi:10.1016/0920-9964(95)00068-2

Schizophrenia Research

Volume 20, Issues 1–2, May 1996, Pages 145-151

https://doi.org/10.1016/0920-9964(95)00068-2 Get rights and content

Abstract

This study examined substance use among a group of 37 schizophrenia patients participating in a year-long fluphenazine decanoate (FD; Prolixin) dosage reduction study (Inderbitzin et al. (1994) Am. J. Psychiatry 151, 1753–1759). Ten (50%) of the 20 FD dose-reduced patients, and 6 (35%) of the 17 control group patients were identified as substance users. The dose-reduced and control groups did not differ significantly in substance use. We examine here the 37 patients regrouped by substance users (n=16) versus non-users (n=21) to determine the effects of substance use. In addition to identifying substance users and types of substances used, we hypothesize that substance users differ demographically from non-users, have worse symptomatology, worse compliance, higher rates of relapse, and therefore, can confound studies. Clinical and demographic data were obtained. At least half of the substance users were using alcohol or cocaine. The substance use group had a significantly higher severity of illness score on the BPRS at study onset. We found no significant differences between the two groups on other rating scales. The non-use group lived more independently, and the substance use group was younger. The substance use group had nearly twice as many hospitalizations in the 2 years prior to the study, a greater rate of missed appointments in the year before and during the study, and 4 times as many relapses during the year of the study than the non-use group. The key finding was that among 9 of the 37 patients who relapsed in the year of the study, 7 of the 9 had a history of substance use. Substance use was found to be a better predictor of relapse and hospitalization than gradual 50% dosage reduction of FD in the related study. Substance use among schizophrenia patients is a major complicating factor.

References (25)

Abnormal Involuntary Movement Scale (AIMS), rev. (1985) Department of Health and Human Services, Public Health Service....
American Psychiatric Association
DSM-III-R: Diagnostic and Statistical Manual of Mental Disorders
(1987)
N.C. Andreasen
Modified Scale for the Assessment of Negative Symptoms (SANS)
(1984)
N.C. Andreasen
Scale for the Assessment of Positive Symptoms (SAPS)
(1984)
S. Arndt et al.
Comorbidity of substance abuse and schizophrenia: the role of pre-morbid adjustment
Psychol. Med.
(1992)
J.G. Barbee et al.
Alcohol and substance abuse among schizophrenic patients presenting to an emergency service
J. Nerv. Ment. Dis.
(1989)
J. Cohen
Statistical Power Analysis for the Behavioral Sciences
(1988)
L. Dixon et al.
Acute effects of drug abuse in schizophrenic patients: clinical observations and patients' self-reports
Schizophr. Bull.
(1990)
R.E. Drake et al.
Substance abuse among the chronic mentally ill
Hosp. Commun. Psychiatry
(1989)
R.E. Drake et al.
Alcohol use and abuse in schizophrenia
J. Nerv. Ment. Dis.
(1989)

M. Hamilton

A rating scale for depression

J. Neurol. Neurosurg. Psychiatry

(1960)

L.B. Inderbitzin et al.

A double-blind dosage reduction trial of fluphenazine decanoate in chronic, unstable schizophrenic patients

Am. J. Psychiatry

(1994)

Cited by (215)

Substance use disorders in schizophrenia: Prevalence, etiology, biomarkers, and treatment
2023, Personalized Medicine in Psychiatry
Substance use disorders (SUDs) are common among individuals with schizophrenia and negatively affect the clinical course of the illness. Despite the high prevalence and significant impact on outcomes, the etiology of SUDs in individuals with schizophrenia remains poorly understood. A better understanding of the etiology, shared mechanisms, temporal evolution, and complex interplay between pathophysiologies will provide the foundation for rational development of targeted therapeutics. We review the literature on the prevalence, etiology, biomarkers, and treatment for individuals with comorbid SUDs and schizophrenia. Substance use is associated with increased risk of subsequent development of schizophrenia. However, the directionality of the relationship between substance use and schizophrenia remains unclear. While several SUDs are associated with increased psychotic symptoms, others are correlated with less severe psychopathology. Individuals with schizophrenia who have more severe symptoms are more likely to have a SUD. There is evidence for shared genetic risk for SUDs and schizophrenia. Comorbid SUDs and schizophrenia share abnormalities in the mesolimbic dopamine system, affecting drug reward, sensitization, and craving. Neuroimaging studies have identified molecular, structural, and functional pathophysiology in co-occurring schizophrenia and SUDs. Neuroinflammation may also represent a shared pathophysiology between SUDs and schizophrenia. While treatments for SUDs exist, they are generally less effective and underutilized for individuals with schizophrenia. Future research is essential to understand the underlying etiology of SUDs in schizophrenia. We propose that neuromodulatory experiments can establish this etiology and identify therapeutic targets. Longitudinal studies across multiple modalities (i.e. neuroimaging, serum, genetics) may help to identify risk factors and biomarkers.
Does theory of mind predict specific domains of social functioning in individuals following a first episode psychosis?
2021, Psychiatry Research
Social functioning is a central aspect in the treatment of people with psychosis, even more so with the recovery movement promoting an optimal life in one's environment. A good ability to function socially is, among other things, associated with fewer future complications and a better overall quality of life. However, prognostic markers currently in use (i.e., cognitive functioning) to predict an individual's subsequent functioning do not always produce conclusive results in individuals who have recently experienced a first episode of psychosis (FEP). The objective of this study was to evaluate the prognostic value of theory of mind in FEP individuals. Thirty-seven individuals who were followed in a FEP clinic were recruited for the study. Multiple linear regressions were performed for data analysis. The results suggest that theory of mind may be, for specific domains of social functioning in this sub-population, a more important predictor than cognitive functioning variables; though studies with larger samples are needed to support these results.
Perspective on medication decisions following remission from first-episode psychosis
2020, Schizophrenia Research
Citation Excerpt :
At baseline, the former study reported a total of about 35% participants with any SA or dependence, whereas only 3% of the latter study had a record of SA. As the use of illicit substances could largely heighten the risk of relapse (Swofford et al., 1996; Gupta et al., 1996), the lower rates of SA at baseline in Hui et al. (2018) could limit the generalizability of its findings to high SA populations and partially account for its conflicting conclusions with Wunderink et al. (2013). The treatment strategies adopted also underlie a major distinction between the two RCTs – one used placebo i.e. AP discontinuation (Chen et al., 2010), and the other applied dose reduction/discontinuation (Wunderink et al., 2007).
While antipsychotics (APs) could provide rapid relief of positive symptoms in psychotic disorders, their usage is often associated with side effects, stigma and inconveniences. For these and other reasons, many psychosis patients, particularly those of first-episode psychosis (FEP) in remission, wish to discontinue maintenance treatment. The current review aims to discuss the strategies of AP treatment following remission from FEP, with particular emphasis on the evaluation of outcomes following AP discontinuation. Upon review of relevant literature, three potential strategies are put forth for treatment-responsive, remitted FEP patients: a) life-long maintenance treatment, b) AP discontinuation during second year of treatment, or c) AP discontinuation after three years of treatment. In theory, the first strategy presents the safest option for maximal symptom control. However, a rigorous RCT indicates that if AP discontinuation is to be attempted, the third strategy best prevents poor long-term clinical outcomes. Further data is needed to address the costs and benefits of each treatment strategy, compare AP-free patients with those on different types of APs, as well as explore even longer-term outcomes.
Effectiveness of Integrated Dual Diagnosis Treatment (IDDT) in severe mental illness outpatients with a co-occurring substance use disorder
2018, Journal of Substance Abuse Treatment
Citation Excerpt :
In comparison, lifetime prevalence of SUD in the general population is 17–19% (de Graaf, Ten Have, & van Dorsselaer, 2010; Regier et al., 1990). The occurrence of co-morbid SUD in schizophrenia has been associated with a variety of negative consequences such as poor social and clinical outcomes, relapse, hospitalisation, psychopathology, treatment non-adherence, distorted perception and cognition, suicidal ideation, social exclusion, homelessness, aggression, legal problems and injury (Drake & Brunette, 1998; Drake, Osher, & Wallach, 1991; Hawton, Sutton, Haw, Sinclair, & Deeks, 2005; Hunt, Bergen, & Bashir, 2002; Miner, Rosenthal, Hellerstein, & Muenz, 1997; Negrete & Knapp, 1986; Ries et al., 2000; Swartz et al., 1998; Swofford, Kasckow, Scheller-Gilkey, & Inderbitzin, 1996). The consequences of co-morbid SUD among SMI patients are well documented and has resulted in the development of several psychosocial interventions.
Integrating substance use disorder treatment with psychiatric treatment is considered more favourable then treating these disorders parallel or sequential, but the evidence base is inconclusive. We examined the effectiveness of Integrated Dual Diagnosis Treatment (IDDT) on substance use in severe mental illness outpatients with substance use disorders. IDDT is a collaborative, multidisciplinary team approach in which motivational interviewing is a key element. In addition, we also examined the effects of IDDT implementation on skills and knowledge of mental health care professionals. A randomized controlled stepped-wedge cluster trial was performed in 6 functional assertive cummunity treatment teams. We included 37 clinicians who were given a three-day IDDT training. Our primary outcome was days of substance use at follow up, 12 months after IDDT implementation. This was assessed in 154 included patients and was measured with the Measurement in the Addiction for Triage and Evaluation. After implementation of IDDT we found a reduction in the number of days patients used alcohol or drugs, but no improvements on other secondary outcomes such as psychopathology, functioning, therapeutic alliance or motivation to change. Also, IDDT training did not seem to improve clinicians' knowledge, attitudes and motivational interviewing skills. Effects on our secondary outcomes may have been limited by the absence of a training effect in our clinicians. Our study clearly underlines the complexity of disseminating IDDT and in particular motivational interviewing.
Neuroendocrine and immune pathways from pre- and perinatal stress to substance abuse
2018, Neurobiology of Stress
Early life adversity is a documented risk factor for substance abuse and addiction. The pre- and perinatal period (i.e., from implantation, through pregnancy, to 6 months of age) is a critical period marked by high biological plasticity and vulnerability, making perinatal stress a particularly robust form of adversity. The neuroendocrine and immune systems are key mechanisms implicated in the transmission of addiction risk. We review animal and human studies that provide preliminary evidence for links between perinatal stress, neuroendocrine and immune dysregulation, and risk for substance abuse and addiction. A translational neuroscience perspective is employed to elucidate pre- and perinatally-induced biological mechanisms linked to addiction and discuss implications for prevention and intervention efforts. Significant evidence supports associations between pre- and perinatal stress and dysregulation of the hypothalamic-pituitary-adrenal axis and immune systems as well as links between neuroendocrine/immune functioning and addiction risk. More work is needed to explicitly examine the interplay between pre- and perinatal stress and neuroendocrine/immune disruptions that together heighten substance abuse risk. Future work is needed to fully understand how pre- and perinatal stress induces biological alterations to predispose individuals to higher risk for addiction. Such knowledge will strengthen theoretically-driven and empirically-supported prevention efforts for substance abuse and addiction.
Inflammation, substance use, psychopathology, and cognition in phase 1 of the clinical antipsychotic trials of intervention effectiveness study
2018, Schizophrenia Research
Schizophrenia has been associated with aberrant blood levels of inflammatory markers. However, patients with comorbid illicit drug use have been inadequately studied with respect to immune function. Furthermore, associations between inflammatory markers, psychopathology, and cognition have been inconsistently considered. We investigated relationships between inflammatory markers, comorbid marijuana and cocaine use, and psychopathology and cognition in patients with schizophrenia.
For subjects with available fasting data from the baseline visit of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial, inflammatory markers were investigated as predictors of psychopathology and cognition in patients with and without comorbid marijuana or cocaine use, using linear regression models controlling for potential confounding factors.
Compared to subjects with a negative urine drug screen (UDS), marijuana use was a predictor of higher lymphocytes and E-selectin, and lower leptin (p ≤ 0.04 for each); cocaine use was a predictor of higher adiponectin (p = 0.04). In subjects with marijuana use, lower WBC and higher IL-6 were predictors of higher PANSS total score (p < 0.05 for each). In subjects with cocaine use, lower total and differential WBC were predictors of higher PANSS total score (p < 0.04 for each). In younger, non-obese subjects with a negative UDS, higher monocytes and IL-6 were predictors of PANSS total score (p < 0.04 for each).
Our findings provide additional evidence that inflammation may be associated with psychopathology and cognition in some patients with schizophrenia. Furthermore, there is preliminary evidence for differential effects of comorbid marijuana and cocaine use on these relationships.

View all citing articles on Scopus

View full text

Research paperSubstance use: a powerful predictor of relapse in schizophrenia

Abstract

DSM-III-R: Diagnostic and Statistical Manual of Mental Disorders

Modified Scale for the Assessment of Negative Symptoms (SANS)

Scale for the Assessment of Positive Symptoms (SAPS)

Comorbidity of substance abuse and schizophrenia: the role of pre-morbid adjustment

Psychol. Med.

Alcohol and substance abuse among schizophrenic patients presenting to an emergency service

J. Nerv. Ment. Dis.

Statistical Power Analysis for the Behavioral Sciences

Acute effects of drug abuse in schizophrenic patients: clinical observations and patients' self-reports

Schizophr. Bull.

Substance abuse among the chronic mentally ill

Hosp. Commun. Psychiatry

Alcohol use and abuse in schizophrenia

J. Nerv. Ment. Dis.

A rating scale for depression

J. Neurol. Neurosurg. Psychiatry

A double-blind dosage reduction trial of fluphenazine decanoate in chronic, unstable schizophrenic patients

Am. J. Psychiatry

Research paper
Substance use: a powerful predictor of relapse in schizophrenia