This systematic review (2016) examined the available literature on novel psychoactive substances with regard to their effects on people with severe mental illness. Analyses yielded mixed results, given that the people used various different types of substances, or even manifested different types of reactions in response to the same substance in one case with four patients who all had schizophrenia. The review highlights a lack of sufficient empiric evidence on the interaction between psychosis, brain dysfunction, prescribed medication, and novel psychoactive substances to establish adverse effects that are specific to mental illnesses.
Abstract
“Introduction: Novel psychoactive substances (NPS) are synthetic substances that have been developed to produce altered states of consciousness and perceptions. People with severe mental illness (SMI) are more likely to use NPS than people without mental illness, but the short‐ and long‐term effects of NPS are largely unknown.
Method: We systematically reviewed the literature about the effects of NPS on people with SMI.
Results: We included 12 case reports, 1 cross‐sectional survey and 1 qualitative study. Participants included mostly males aged between 20 and 35 years. A variety of NPS were used, including synthetic cathinones and herbs such as Salvia. The most commonly reported effects of NPS were psychotic symptoms (in some cases novel in form and content to the patients’ usual symptoms) and significant changes in behaviour, including agitation, aggression and violence. Patients’ vital signs, such as blood pressure, pulse rate and temperature, were also commonly affected.
Conclusion: NPS potentially have serious effects on people with SMI, but our findings have limited generalizability due to a reliance on case studies. There is a paucity of evidence about the long‐term effects of these substances. Further research is required to provide a better understanding about how different NPS affect patients’ mental and physical health.”
Authors: Richard Gray, Daniel Bressington, E. Hughes & A. Ivanecka
Summary
Novel psychoactive substances (NPS) include synthetic drugs mimicking the effects of illicit drugs, and herbs such as Salvia divinorum. Little is known about the effects of NPS on people with severe mental illness, and little is known about the long-term consequences of NPS use on the mental and physical health of SMI patients.
Abstract
We reviewed 12 case reports, 1 cross-sectional survey and 1 qualitative study about the effects of novel psychoactive substances on people with severe mental illness.
Background
People with severe mental illness, such as schizophrenia and bipolar disorder, are at increased risk of suffering co-morbid conditions including substance misuse. People with a dual diagnosis have worse clinical outcomes.
In recent years, new drugs and drug substitutes have emerged, possibly in response to the increased control of illicit drugs. At least 5% of young people aged 15-24 in the EU have tried novel psychoactive substances.
NPS are drugs that are not currently controlled by the UN’s 1961 Narcotic Drugs/1971 Psychotropic Substances Conventions, but can pose a public health threat comparable to that posed by substances listed in these conventions. They can cause hallucinations, agitation, tachycardia, hypertension, vomiting, seizures, stroke, rhabdomyolysis, kidney injuries and death.
Dopamine is a neurotransmitter involved in controlling behaviours and thought processes, and its function is disturbed when certain NPS are used, triggering their psychoactive effects. It might be hypothesized that NPS use in people with SMI could have stronger and more severe effects.
Methodology
We searched for literature related to novel psychoactive substances and SMI using the following keywords: new psychoactive substances, legal highs, designer drugs, research chemicals, smart drugs, emerging drugs of abuse.
Inclusion criteria
We included studies using any research design on how exposure to NPS affects mental and physical health of people with a current diagnosis of SMI.
Participants
Studies were included if the participant(s) were diagnosed with a SMI (schizophrenia, delusional/ psychotic illness, or bipolar disorder) and the diagnosis was established by a gold-standard structured clinical interview.
Exposure
We included studies where participants reported having used NPS, which are not currently controlled by the UN. No comparator was defined for this review.
Study selection and data extraction
We identified studies in the literature on the effects of NPS on health and mental health. We developed a data extraction tool and piloted it on a sample of studies to check its utility.
Risk of bias and quality assessment
We assessed the risk of bias and methodological quality of studies using different validated ROB assessment tools, and the results were reported to inform the interpretation of the findings.
Results
After removing duplicates and non-English papers, we assessed 133 articles for eligibility, excluding 119 articles because their focus was not on SMI. We included 12 full studies and 2 conference abstracts that met our inclusion criteria.
Study description
Thirteen studies were included in this review, including 10 single case reports, 2 case series and 1 study involving qualitative interviews with NPS users about their experiences with the substances. Seven studies were conducted in Europe, three in the United States, one in India and two studies were in other countries.
Risk of bias and quality of the studies
The 12 case studies included in this review were assessed using the Newcastle-Ottawa quality assessment scale for case – control studies, because there were no appropriate assessment tools for noncomparative case reports. The studies were subject to relatively high inherent ROB due to involving a small number of participants.
We included one qualitative study and one cross-sectional survey. The qualitative study had a relatively high risk of bias due to not providing enough detail regarding the recruitment process, exploration of the relationship between the researcher and participants during data collection and how thematic analysis was undertaken.
Participants
The case studies included in this review involved a total of 19 participants, of whom 17 had prior SMI. The majority of participants were male and the mean age was 31 years.
The qualitative study included 21 participants, of which 15 were eligible for this review. Of these, 15 had psychotic disorders and 23 had purchased NPS in specialized drug shops called ‘head shops’.
Exposure: NPS used in the included studies
Most participants had used bath salts, four had used a synthetic cannabinoid called AM-2201, and six had used other types of substances. All participants had used the same type of synthetic cannabinoid, called JWH-018.
Short-term effects
In 17 cases, patients reported psychotic symptoms after taking NPS, including delusions, hallucinations, severe thought disorder and altered mental status. Participants in a qualitative study perceived NPS as less harmful or ‘natural’ substances that ‘make you high’ in a faster and safer way compared to illicit drugs.
Patients’ behaviour after the use of NPS was severely affected, with 9 exhibiting bizarre or chaotic behaviour, 5 requiring chemical and/or physical restraint, and 3 displaying violent, aggressive or assaultive behaviour.
Effects on physical health
Nine of 17 patients had significant change in vital signs, most often elevated heart rate, blood pressure, increased temperature and profuse sweating, symptoms reported to be consistent with serotonin syndrome. Six patients had renal impairment and two had liver function damage requiring treatment in intensive care.
Long-term effects
Six patients recovered within 2-12 hours, two more recovered on day 3 and 4, and three patients were still unwell or just improved after 1 month of intoxication.
Out of 17 cases, one death was reported. The author hypothesized that the death was caused by a severe reaction to the pepper spray.
How was NSP use confirmed?
The case studies provided little or no detail about how NPS use was objectively confirmed. Most patients reported taking drugs based on self-report, but two patients denied taking drugs at first.
Only 5 of 12 authors reported having done any testing of the substances used. In seven cases a standard urine drug/toxicology screen was performed, usually negative for the NPS taken by the patient.
Discussion
This review aimed to investigate evidence of the effects of NPS for people with serious mental illness. The results showed that most participants experienced significant changes in vital signs and often significant and rapid alteration of mental status, involving psychotic symptoms and bizarre behaviour.
We observed the effects of NPS in patients with psychosis, brain dysfunction, prescribed medication and in the general population, but did not identify any positive effects.
We suggest that NPS can have a relatively severe effect on people with psychotic disorders. The effects on mental health may differ between the general population and the SMI population, and NPS-related aggression may negatively influence future mental health treatment or hinder recovery.
It is likely that the full extent of NPS use by people with SMI is under-recognized, and that many people with SMI believe NPS are less harmful than illegal substances or are ‘natural’. Therefore, mental health and other health-care professionals should routinely enquire about NPS use by people with SMI.
This systematic review indicates that NPS may have serious effects on the mental and physical health of people with serious mental illness.
Review limitations
This review had several limitations, including that most papers were case studies and a cohort study, which are inherently more likely to be of a lower quality and high ROB. Additionally, some papers lacked details about patients’ clinical history and long-term follow-up.
The small number of studies included in this review suggests that the issue of NPS use among people with SMI may be under-reported and/or under-researched, and more evidence is needed to inform clinical decisions and policy making.
Clinical recommendations
Patients might not perceive NPS use as ‘drug use’ and may not know the likely effects and risks involved in their use. Health professionals should be vigilant and actively enquire about illicit as well as NPS drug use by people with SMI.
Research recommendations
Our review suggests that NPS use may have serious and potentially lethal consequences for some people with SMI, but more research is required to provide a better understanding of the short- and long-term effects of NPS.
More observational and prevalence research is needed to determine the effects of NPS on people with SMI.
Author contribution
The study was conceived by RG, DB and EH, and AM conducted the initial literature search.