Brain imaging studies
Critics of psychiatric drugs, such as Peter Breggin have long been arguing
that neuroleptic drugs damage the brain (Breggin 1993b, 1997).
He argued that the reduced brain volume found in patients with schizophrenia
was evidence of drug-induced damage, rather than the official
explanation that it was attributable to the process of schizophrenia. Two
new studies support Breggin’s interpretation. In 2005 results of the
largest ever brain-imaging study of people with first episode psychosis
was published in the American Journal of Psychiatry. The study was
funded by Eli Lilly the makers of the ‘atypical’ neuroleptic drug olanzapine
(Zyprexa) and involved 161 patients who were randomised to
treatment with haloperidol or olanzapine (Lieberman et al. 2005b).
Magnetic resonance imaging (MRI) scans were conducted at the start of
the randomised treatment and then periodically thereafter and compared
with scans from a matched group of 58 controls. The results
demonstrate that even after 12 weeks of haloperidol treatment there
was a statistically significant reduction in the grey matter in the brain3
compared with controls (p.005). After one year the difference was
even greater (p.003). The results show that olanzapine-treated subjects
also had a reduction of overall grey matter volume after one year
(p .03) with evidence of reductions in frontal, parietal and occipital
lobes of the brain. The olanzapine-treated group also showed reduced
volume of the caudate nucleus after one year compared with controls
(p.003) and compared with haloperidol-treated patients (p.02). The
text of the study glosses over the effects of olanzapine, reflecting the
interests of the sponsors. In fact, the authors only briefly admit the possibility
that the effects may have been due to the drugs, focusing instead
on the possibility that olanzapine may prevent the decline in brain volume
associated with schizophrenia better than haloperidol!
However a second shorter study confirms that these effects are most
probably attributable to the drugs. A group of researchers at the Institute
of Psychiatry in London studied a group of 84 patients with first episode
psychosis after 8–9 weeks of neuroleptic drug treatment (Dazzan et al.
2005). They found that compared with patients who were psychotic but
not taking neuroleptics, patients who were taking older or ‘typical’
antipsychotics had reduced volume of grey matter in several brain areas
and enlargement of the basal ganglia. Both findings were significantly
associated with neuroleptic dose. Correlation with dose is traditionally
taken as strong evidence of a causal effect in medical epidemiology.
Atypical antipsychotics were associated only with enlargement of the
thalamus,4 a finding that was also correlated with dose. The exposure
period may have been too short at nine weeks to detect other changes
in this group. The findings may also have been more marked if the
comparison group was restricted to patients who had never had neuroleptics,
since about half of the group had had previous exposure.
Traditionally the atrophy of the brain observed in people with schizophrenia
has been attributed to the process of schizophrenia itself and
has been regarded as confirmatory evidence that schizophrenia is a
brain disease involving neurodegeneration. Research on brain structure
barely mentions the possibility that drugs may produce or exaggerate
brain changes even though most studies involve patients who have
received many years of neuroleptic and other drug treatment. For
example, a study published in the British Journal of Psychiatry in 2005
revealed substantial deficits of grey matter (nerve cell bodies) and white
matter (nerve fibres) in brains of long-term patients diagnosed with
schizophrenia compared with age-matched healthy controls. Multiple
brain regions were affected including the frontal cortex, the cerebellum,
the temporal cortex, the basal ganglia, the thalamus and parts of the
parietal lobe (McDonald et al. 2005). Patients with bipolar disorder, in
contrast, showed deficits in white matter only. Despite the fact that all
patients with schizophrenia were taking antipsychotic drugs and had
most probably been taking them for a considerable time, there is no
mention of the possibility that drug exposure might have been responsible
for the reduced grey matter. No attempt is made to examine correlations
between drug exposure and brain volume in the statistical
analysis, which would have been a relatively simple procedure. The
only mention of drugs is a sentence in the discussion section of the
paper, which refers to the possibility that psychotropic drug exposure
might account for white matter deficits. Why it should account for
white matter but not grey matter deficits is not indicated and I can
think of no plausible explanation.
Despite the common indifference to the possibility that drugs may
affect brain structure illustrated by this paper, several studies have looked
at patients with a first episode of psychosis or schizophrenia, partly to try
and minimise the confounding effects of drugs. None of these studies
was entirely restricted to patients who had never taken psychiatric medication
before and where it was examined, a statistically significant correlation
between exposure to neuroleptics and reductions in grey matter
volume was found (Cahn et al. 2002; DeLisi et al. 1991; Gur et al. 1998).
A recent meta-analysis of some MRI studies of first episode patients compared
with normal volunteers found reduced brain volume and enlarged
brain ventricles (cavities) in patients with psychosis, but the authors
emphasised that the overall differences were so small that they were
‘close to the limit of detection by MRI methods’ (Steen et al. 2006, p.
510). In the Discussion section of the published paper they did acknowledge
the possibility that the effects might be a result of early antipsychotic
drug treatment, but this was not mentioned in the Abstract,
which suggested that the study demonstrated that schizophrenia was a
‘neurodegenerative’ or ‘neurodevelopmental’ process. Curiously, the
paper did not cite the results of the Lilly-funded first episode study of
brain structure, and nor did they include data from this study in the
meta-analysis, even though the first author of that study, Jeffrey
Lieberman, was also one of the authors of the meta-analysis. Another
review that specifically examined MRI evidence of drug-induced effects
did include the Lilly study but it emphasised the superiority of atypical...
Myth of Chemical Cure, J.Moncrieff (pdfko zde ke stazeni v auditku)