The impact of untreated psychosis in low and middle income (LAMI)countries and a paradigm for early intervention.

ABSTRACT
This thesis is based on 13 papers published in peer reviewed journals. These include studies
on epidemiology and treatment of major psychotic disorders, and metanalysis of studies on
Duration of Untreated Psychosis (DUP) and its relationship with the Gross Domestic
Product and the outcome in Low and Middle Income (LAMI) countries. Based on this
research that highlighted the extent and impact of untreated psychosis, a series of papers
presented a novel approach for early intervention in psychosis in LAMI countries. The final
paper presents the randomised controlled trial evaluating this approach.
Seven publications on puerperal psychosis, homicide by patients suffering from
Schizophrenia, and the impact of cannabis use on symptomatology and course of
schizophrenia highlighted significant gaps in the care of schizophrenia in developing
countries. Only 12 patients (24%), charged with homicide had received some form of
treatment before the index crime, despite the fact that duration of illness was more than 5
years in most cases. In a clinical sample of 35 patients suffering from acute episode of
Puerperal psychosis the mean time between the onset of symptoms and receiving
psychiatric care was almost a month. Two third of mothers suffering from Puerperal
psychosis could not breast feed, most showing almost total lack of concern for the baby and
also other behavior which could result in harm to baby. The publications on Puerperal
psychosis argued that prevention of the disorder should be feasible in developing countries
in view of high incidence of the disorder following an identifiable life event (childbirth)
and the fact that most of the risk factors could be screened in the antenatal period.
A paper published in British Journal of Psychiatry estimated the Duration of Untreated
Psychosis (DUP) and its impact on the outcome of psychosis. Based on metanalysis of 98
studies (23 from LAMI countries and 75 were from high-income countries) the DUP of
LAMI countries (125 weeks) was twice as long as the DUP in high-income countries (63
weeks, p=0.012). The relationship between DUP and the gross domestic product (GDP)
purchasing power parity was also examined using the data from International Monetary
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Fund (IMF) and the World Bank. There was a strong negative correlation between DUP
and GDP ppp, indicating that for every thousand dollars of additional GDP (purchasing
power parity), mean DUP was reduced by 8 weeks and median DUP was reduced by 5
weeks.
A study published in Schizophrenia Research examined the association between DUP and
at least one of the following outcome measures; psychotic symptoms, cognitive function,
social disability or mortality. Patients with a longer DUP had a smaller reduction in
symptom scores after treatment when compared to patients with shorter DUP. The pooled
estimate indicated that longer DUP was negatively associated with the degree of reduction
in symptom scores (random effects Meta analysis; r=−0.290, 95% CI=−0.483 to−0.069,
z=−2.559, P < 0.011) and longer DUP was associated with greater level of disability (fixed
effects Meta analysis; r=0.195, 95% CI=0.126 to 0.262, z=5.498, p<0.000; heterogeneity
Q-value 1.245, p=NS, I2=0.00).
These studies clearly established the case for Early Intervention in psychosis. However, an
entirely different approach was needed for this in resource poor settings. This approach is
described in three papers. This approach termed as ‘Supervised Treatment of Outpatient
Schizophrenia’ (STOPS) was evaluated in a Randomized Controlled Trial. The paper
describing this RCT which provided proof of the concept will soon be published by British
Journal of Psychiatry. In this RCT, fifty five patients were recruited in each arm. Ninety
five (86.36%) patients completed the study; 49 in STOPS and 46 in Treatment As Usual
(TAU) group. At one year follow up, 37 (67.3%) patients in STOPS group had complete
adherence with medication compared to 25 (45.5%) in the TAU group (P<.02). The
patients in STOPS group also showed more improvement in symptoms (P=0.003) and
functioning (P<0.011).