Secondary Schizophrenia (53 page)

descending dorsal diencephalic system (consisting of
A small series of 10 patients with comorbid
stria meduIlaris, habenula, and fasciculus retroflexus),
schizophrenia and drug use were treated with arip-is an important link between limbic and striatal
iprazole for 8 weeks in an open-label design
[76].
In
forebrain and lower diencephalic and mesencephalic
those who completed the trial (60%), positive urine
centres. Studies of glucose utilization have consis-drug tests dropped significantly after 2 weeks. Both
tently shown the habenula to be highly sensitive to
mean cocaine and alcohol craving scores also dropped
dopamine agonists and antagonists. Lesions of habe-significantly with a positive correlation between drop-nula produce a wide variety of behavioral alterations.

ping psychosis and dropping craving scores. Green
The dorsal diencephalic system has major and pre-and colleagues
[77]
examined the acute response to
dominantly inhibitory connections onto dopamine-haloperidol and olanzapine in 97 first episode psy-containing cells and it mediates part of the negative
chosis patients with comorbid substance abuse. They
feedback from dopamine receptors onto dopamine cell
found no difference between typical and atypical med-bodies. It represents one of the major inputs in brain
ications but an overall less likelihood of responding
to the raphe nuclei and has anatomical and functional
when compared to patients without drug use comor-connections to modulate important functions such as
bidity. These findings are in contrast to a report by
sensory gating through thalamus, pain gating through
Brown and colleagues
[78]
of 24 dually diagnosed
central grey and raphe and motor stereotypies and
patients who were on typical antipsychotics and were
reward mechanisms through substantia nigra and the
randomized to either continue or discontinue the
ventral tegmental area. Alterations in these pathways
drug. Quetiapine was substituted when necessary in
are ideal candidates for producing the behaviors that
those who discontinued the typical antipsychotic. They
occur during psychosis and that future considerations
report that those discontinuing a typical antipsychotic
of the circuitry underlying psychoses need to include
had a significant reduction in drug craving as com-this important but less examined system.

pared to the other patients. Brown and colleagues further reported that typical antipsychotic discontinuation combined with a quetiapine switch was associated
Available insights into the

with reduced drug craving. Finally, animal work sug-

management of stimulant-induced

gests a possible role for serotonin in treating this condition. When cocaine and risperidone were coadmin-

psychotic conditions

istered to rats, the effects of cocaine seemed to have
There is indeed a paucity of data regarding treatment
been blocked
[79].

for MAP, with a complete lack of controlled treatment
Current research indicates that people present-trials, including head-to-head comparison to nondrug
ing with co-occurring disorders, such as MAP, war-induced psychotic patients
[18].
The currently prevail-rant specific treatments that deal with both the
ing standard of care in this area parallels the manage-psychosis and addiction issues
[18].
In fact, the best
135

ment of acute psychosis from other etiologies, such
outcomes stem from programs that are considered
Organic Syndromes of Schizophrenia – Section 3

evidence based and that integrate mental health and
Based on a stress-diathesis model, we propose that
substance abuse treatment. Barr and colleagues noted
the eventual development of a chronic psychotic disor-that most MA treatments investigated so far have used
der in an individual with a history of drug use is likely
only an “addiction” treatment model for stimulant
to be multifactorial with the specific substances used,
dependence and have excluded people with comorbid
the pattern of use (including duration and age of onset
mental health problems, such as persistent or recur-of regular use, dose and pattern of episodes of use),
rent psychotic symptoms. Further research is required
and environmental stress interacting with the indi-to develop a more thorough understanding of the pro-vidual’s own degree of psychosis proneness to gener-files of people who suffer from persistent or recurrent
ate different degrees of severity of psychotic processes
MAP.

[82].
It is quite possible that the combination of drugs
If sensitization is indeed the underlying mech-used, possibly with the exceptions of MA and hallu-anism for psychostimulants-induced psychosis, then
cinogens that seem to be capable of producing chronic
early treatment and retention of stimulant users in
psychotic syndromes on their own, is a crucial factor
mental health care services would appear to be desir-in the nature of the emergent pathology.

able to prevent the development of a chronic psychotic
A number of factors may contribute to the even-condition. There is indeed a lack of good quality evi-tual development of a psychotic state. The fact that
dence as to whether this approach can be effective.

some evidence of abnormality may be evident up to
A review by Cochrane found no relevant trials
[80].

10 years prior to onset of frank symptoms makes
A potentially important finding in rats, without par-the task of disentangling these factors extremely chal-allel human studies as yet, is the demonstration that
lenging
[83].
Despite this chicken-and-egg problem,
low-dose clozapine or haloperidol can block the induc-work by Hafner and colleagues [83] showed that a
tion of behavioral sensitization to amphetamine in rats
rather accurate determination of the onset of behav-

[81].
This finding has potential implication for future
ioral change can be determined. This allows the close
preventive use of such drugs in individuals with evi-examination of the chronological associations of drug
dence of increased susceptibility to developing a psy-use and the development of psychotic or even prodro-chotic disorder.

mal schizophrenia symptoms.

It is clear that much research is necessary in order
to answer the many remaining unanswered questions.

Conclusion

The most obvious need is for the development of
Based on the earlier review, it can be proposed that
cohorts of well-characterized patients that can be fol-there is enough suggestive evidence that abuse of psy-lowed longitudinally from the time of first contact.

chostimulants can result in or increase the suscepti-Although obviously not an easy task, it is necessary to
bility for a state of chronic psychosis. It can also be
establish the natural course of these syndromes par-concluded that abuse of amphetamines, as the sole
ticularly in the absence of continued drug use. Many
drug of abuse, can result in a chronic psychotic dis-crucial factors must be characterized in these individ-order. On the other hand, the evidence for a cocaine-uals, including an estimate of genetic risk (i.e. fam-induced chronic psychosis is less compelling. The exact
ily history) and other risk factors (e.g. head injury,
relationships between premorbid vulnerability and the
child abuse, ADD/ADHD). Once well-defined cohorts
persistence of symptoms in the absence of continued
are established, other neuro-investigative (neuropsy-drug use or the degree of use needed to sustain a psychological, electrophysiological, or imaging) as well as
chotic syndrome are also not yet well characterized.

treatment studies can be more easily performed.

136

Chapter 9 – Stimulants and psychosis

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