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OPINION Psychosis induced by amphetamines
Jørgen G. Bramness a and Eline B. Rognli a,b,c
Purpose of review
The study reviews publications on the use of methamphetamine and amphetamine in relation to psychotic
symptoms, substance-induced psychosis, and primary psychosis published between July 2014 and
December 2015. The databases MEDLINE, Embase, and PsycINFO were searched using the terms
‘amphetamine psychosis’ and ‘methamphetamine psychosis’ for the time period 1 July 2014 to 31
December 2015.
Recent findings
There were 37 studies published on the subject during this time period. Risk factors for psychotic symptoms,
substance-induced psychosis, and primary psychosis included patterns of drug use, but results also pointed
to the importance of nondrug-related vulnerability. Cognitive impairment is associated with both
amphetamine use and psychosis, and the impairment among those with amphetamine-induced psychosis
resembles that of schizophrenia. At the neuronal level, GABAergic mechanisms may offer some
understanding about the association between stimulant use and psychosis. Several different types of
antipsychotic medication are effective for treating agitation and psychosis, but drugs with high DRD2
blockade should be used with caution. Some novel treatments are described, but are not sufficiently
repeated to be recommended.
Summary
During the past 18 months, studies have been published that cover risk factors, neuronal mechanisms, and
treatment. These recent results do not differ from previous understandings, but the role of cognition and
GABAergic dysfunction should be further investigated, and knowledge about resilience factors is still
scarce. Also, a clearer evidence base for medical treatment of psychosis with concurrent amphetamine use
is warranted.
Video abstract
http://links.lww.com/YCO/A33
Keywords
amphetamine, drug treatment, methamphetamine, neurobiology, psychosis
ADHD, 2
Drug use in
psychosis, 3
Cognition, 4
Treatment, 4
Comparison with
Prefrontal cortex, 3 schizophrenia, 5
Transition, 1
Comorbidity, 1
GABA, 2
FIGURE 1. Studies on psychosis following use of amphetamines from 1 July 2014 to 31 December 2015 by theme (N ¼ 37).
Broad categories are chosen, but one study may belong to more than one category. Review studies are only belonging to
review category as they often contain information on several points of interest.
0951-7367 Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved. www.co-psychiatry.com 237
Two studies show similar cognitive impairment partially compares this with schizophrenia, offering
in those with psychosis induced either by amphet- a description of the potential neuronal mechanisms
amines or by schizophrenia [14,15]. A study involved in the transition from drug-induced psy-
using inhibition tasks found great similarities chosis to schizophrenia. Earlier theories have
in the ventrolateral prefrontal cortex, suggesting suggested that the presence of free monoamines
similarities in the underlying pathophysiology of in axonal terminals because of amphetamines’ inhi-
psychosis induced by amphetamines and by schizo- bition of the vesicular monoamine transporter of
phrenia [22]. However, both this and another study the monoaminergic cells could result in neuronal
found that, despite great similarities, there are also apoptosis [30]. This could elucidate sensitization to
subtle differences in the prefrontal cortex [23]. the psychotic effects of amphetamines and ulti-
Those with methamphetamine-induced psychosis mately the transition to primary psychosis or
show a similar age of onset of methamphetamine chronic amphetamine-induced psychosis as is the
use and the same frequency of current substance use preferred terminology and understanding in Asia
&
as those with primary psychosis [24 ], but the former [8]. Hsieh and coworkers suggest an alternative
have fewer hospital admissions and lower use of model where the excessive enhancement of dopa-
antipsychotics despite similar severity of psychotic minergic pathways leads to glutamate overflow
symptoms. In all other respects, the two groups in the cerebral cortex, damaging GABAergic inter-
looked quite similar. neurons in the cerebral cortex. The loss of GABA-
ergic interneurons in the cerebral cortex leads
Transition to primary psychosis to dysregulation of glutamate in the cortex precip-
&
0951-7367 Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved. www.co-psychiatry.com 239
is more effective in treating positive symptoms risk factors. Also, further research on prefrontal
than aripiprazole, but may be less tolerated because cortex and possible GABAergic deficits would be
of its purer DRD2 profile [34]. of interest in identifying vulnerable individuals.
As atypical antipsychotics may interfere with
QTc time, it could be that their use should Acknowledgements
be restricted in the acute phase, while the heart is All the work included in this study was performed by the
still affected by amphetamines, to prevent increased two coauthors.
risk of cardiovascular events [37,38]. In the immedi-
ate acute phase, the use of benzodiazepines will be Financial support and sponsorship
a good alternative [39] and is recommended in None.
guidelines [40,41]. However, the updated review
identified only one case series and one case report Conflicts of interest
using benzodiazepines, leading to the conclusion
There are no conflicts of interest.
that benzodiazepines may be adequate for control-
ling agitation, but less evidence is available for their
use in treating psychosis [34]. REFERENCES AND RECOMMENDED
The review also identified one case report using READING
a a2-adrenergic agonist [34] and we found one study Papers of particular interest, published within the annual period of review, have
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