Cornblatt BA, Lencz T, Smith CW, Olsen R, Auther AM, Nakayama E et al. Can antidepressants be used to treat the schizophrenia prodrome? Results of a prospective, naturalistic treatment study of adolescents. J Clin Psychiatry 68: 546-557
This study reports the results of a prospective, naturalistic treatment study of adolescents considered to be in the prodromal (i.e., prepsychotic) phase of schizophrenia.
Forty-eight adolescents (mean age = 15.8 years) participating in the initial phase of the Recognition and Prevention (RAP) program (1998-2005) were included in the current report. Individuals were selected from the overall sample (N = 152) if they had: (1) displayed attenuated positive symptoms, (2) been treated pharmacologically for at least 8 weeks, and (3) been followed up for at least 6 months (mean follow-up = 30.5 months).
Two types of medication were naturalistically prescribed: antidepressants (N = 20) or second-generation antipsychotics (N = 28), with polypharmacy common. The 2 treatment groups did not differ in baseline symptom profiles, with the exception of disorganized thinking, which was more severe in second-generation antipsychotic-treated adolescents. Twelve of the 48 adolescents (25%) developed a psychotic disorder, with all converters having been prescribed second-generation antipsychotics. There were no conversions among antidepressant-treated adolescents (log-rank chi(2) = 7.36, df = 1, p = .007). Treatment outcome, however, was confounded, since 11 of the 12 converters were nonadherent. Adolescents, in general, were more likely to be nonadherent to second-generation antipsychotics (61%, 17/28) than to antidepressants (20%, 4/20; chi(2) = 7.86, p = .005). Improvement in 3 of 5 positive symptoms over time was significant (p < .001) and similar for both medications. Disorganized thought, however, did not improve regardless of treatment.
Nonrandom assignment limits comparisons between antidepressants and anti-psychotics in this study. However, with follow-up, a number of adolescents meeting criteria for prodromal schizophrenia were successfully treated with antidepressants. At present, a substantial number of false positives among the antidepressant-treated subgroup cannot be ruled out. However, the findings suggest that, in some cases, it might be preferable to begin treatment with antidepressants and progress to antipsychotics once symptoms intensify, since adherence to the latter is difficult to maintain.
"Negative symptoms group into two factors, one involving diminished expression of affect and alogia and the second involving avolition, including anhedonia and asociality (Fusar-Poli et al., 2014b). Antidepressants may have a potential benefit for ARMS individuals , as they may target their negative attenuated psychotic symptoms (Cornblatt et al., 2007; Fusar-Poli et al., 2007). These studies indicate that antidepressant treatments in ARMS individuals can impact their longitudinal outcomes. "
[Show abstract][Hide abstract] ABSTRACT: Individuals with at-risk mental state for psychosis (ARMS) often suffer from depressive and anxiety symptoms, which are clinically similar to the negative symptomatology described for psychosis. Thus, many ARMS individuals are already being treated with antidepressant medication.
To investigate clinical and structural differences between psychosis high-risk individuals with or without antidepressants.
We compared ARMS individuals currently receiving antidepressants (ARMS-AD; n = 18), ARMS individuals not receiving antidepressants (ARMS-nonAD; n = 31) and healthy subjects (HC; n = 24), in terms of brain structure abnormalities, using voxel-based morphometry. We also performed region of interest analysis for the hippocampus, anterior cingulate cortex, amygdala and precuneus.
The ARMS-AD had higher 'depression' and lower 'motor hyperactivity' scores than the ARMS-nonAD. Compared to HC, there was significantly less GMV in the middle frontal gyrus in the whole ARMS cohort and in the superior frontal gyrus in the ARMS-AD subgroup. Compared to ARMS-nonAD, the ARMS-AD group showed more gray matter volume (GMV) in the left superior parietal lobe, but less GMV in the left hippocampus and the right precuneus. We found a significant negative correlation between attenuated negative symptoms and hippocampal volume in the whole ARMS cohort.
Reduced GMV in the hippocampus and precuneus is associated with short-term antidepressant medication and more severe depressive symptoms. Hippocampal volume is further negatively correlated with attenuated negative psychotic symptoms. Longitudinal studies are needed to distinguish whether hippocampal volume deficits in the ARMS are related to attenuated negative psychotic symptoms or to antidepressant action.
"Conflicting results were also provided by clinical trials exploring the efficacy of antidepressant drugs in preventing psychosis.76–78 A first naturalistic study indicated that no conversion to psychosis could be detected in 20 prodromal patients receiving antidepressant therapies, while 43% of patients treated with antipsychotic drugs developed a full-blown psychosis over the next 2 years.76 A second retrospective naturalistic study found that 8% of UHR individuals treated with antidepressant drugs became psychotic in the following 2 years, while 29% of patients who received antipsychotic drugs subsequently developed psychosis.77 "
[Show abstract][Hide abstract] ABSTRACT: In the last few decades, substantial research has focused on the possibility of early detection and prevention of the first psychotic episode in young individuals at risk of developing this mental disturbance; however, unresolved clinical and ethical issues still call for further investigations. New perspectives and opportunities may come from the identification of selective psychopathological and instrumental markers linking the appearance of subtle psychotic symptoms with the clinical outcome of specific mental pathologies. Furthermore, empirically derived algorithms and risk staging models should facilitate the identification of targeted prevention therapies, possibly improving the efficacy of well-tolerated therapeutic approaches, such as psychological interventions and natural compound supplementations. To date, the collected evidence on the efficacy and tolerability of pharmacological prevention therapies raises more doubts than hopes. A very early detection of risk and appropriate symptomatic pattern classifications may provide a chance to better match prevention strategies with the development of psychosis.
"Yet, limited evidence exists to provide clinical guidance for use of anti-depressant medications, especially selective serotonin reuptake inhibitors (SSRIs). Meta-analyses exploring use of anti-depressants for people with depression and schizophrenia have been largely inconclusive or have provided limited evidence, at least in part because studies in this area have been limited by samples of fewer than 50. "
[Show abstract][Hide abstract] ABSTRACT: It remains unclear how augmenting anti-psychotic medications with anti-depressants impacts primary positive and negative symptoms of schizophrenia. In this study, we used data collected from a randomized trial comparing citalopram to placebo for management of subsyndromal depression (SSD) in schizophrenia and schizoaffective disorder, to assess the effects of antidepressant augmentation on positive and negative symptoms.
Participants in this study conducted at the University of California, San Diego and the University of Cincinnati, were persons with schizophrenia or schizoaffective disorder aged 40 or older and who met study criteria for SSD. Patients were randomly assigned to flexible-dose treatment with citalopram or placebo augmentation of their current anti-psychotic medication. Analysis of covariance was used to compare changes in positive and negative syndrome scale (PANSS) scores between treatment groups. We also assessed mediating effects of improvement in depression and moderating effects of multiple factors on positive and negative symptoms.
There was significant improvement in PANSS negative symptoms scores in the citalopram group, which was partially mediated by improvement in depressive symptoms. There was no effect on PANSS positive scores.
In patients with schizophrenia/schizoaffective disorder, treating depressive symptoms with citalopram appears to carry the added benefit of improving negative symptoms.
Indian Journal of Psychiatry 04/2013; 55(2):144-8. DOI:10.4103/0019-5545.111452
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