How are the adverse effects of specific classes of antidepressants (SSRIs in particular) comparable with the effects of certain dopamine agonists (e.g. amantadine) that are disputatiously believed to exacerbate positive symptoms of schizophrenia (e.g. delusions and hallucinations)?
Thanks Michael.
However, the biochemical mechanisms underlying such adverse effects of SSRIs and the ironic similarity of those effects to those of the mentioned dopamine agonists have led to rather ambiguous and controversial clinical results.
Since dopamine agonists and SSRIs act via disparate neurotransmitter systems; what I would like to see more is further comments regarding the potential or alternative hypothesis about such paradoxical yet similar effects of SSRIs compared to dopamine agonists on unexpected exacerbation of positive symptoms of schizophrenia.
This paper may help you. perhaps the researchers are here on RG:
Randomized Controlled Trials of Add-On Antidepressants in Schizophrenia
Viacheslav Terevnikov, MD, PhD Grigori Joffe, MD, PhD Jan-Henry Stenberg, PhD
International Journal of Neuropsychopharmacology, Volume 18, Issue 9, July 2015, pyv049, https://doi.org/10.1093/ijnp/pyv049
“Antidepressants in the Treatment of Positive Symptoms of Schizophrenia
Antidepressants seem to have no desirable effect on positive symptoms of schizophrenia, as almost all RCTs were disappointing in this respect. The only exception was a study by Joffe and coauthors (2009), in which mirtazapine (but not placebo) added to on-going therapy with various FGAs improved positive symptoms. This result diverged from other mirtazapine trials. It is possible that in that particular study, the researchers succeeded in minimizing the regression to the mean by a sound process of stabilization of clinical status and dosage of the FGAs. Also, placebo response and low adherence to the protocol procedures were minimized by a placebo run-in period, which probably explained the high patient retention level. Stabilization and low drop-out rate might permit for surfacing a possible additive antipsychotic effect of mirtazapine. This observation, however, has to be replicated in other studies with similarly rigorous methodology.
In clinical practice, physicians are sometimes concerned with a risk of worsening or exacerbation of psychosis when prescribing antidepressants to patients with schizophrenia (Petit, 1994). Moreover, some current schizophrenia treatment guidelines suggest caution when using antidepressants (APA, 2004). This review does not support this opinion, since not a single study with an add-on antidepressant reported worsening of positive symptoms. The majority of the presented RCTs, however, involved subjects with chronic schizophrenia, with only 3 trials comprising acutely ill subjects. It therefore remains unclear to what extent this observation can be extrapolated to acute schizophrenia.”
Thanks Beatrice for sharing this paper on the Mirtazapine and in general antidepressant-induced chronic positive symptoms of schizophrenia.
This also indicates that specific classes of antidepressant such as Mirtazapine may not only exacerbate certain positive symptoms of schizophrenia, but also may increase the tendency to attempt suicide in those who are more prone to mania and psychosis.
However, as I mentioned it has been observed that dopamine agonists such as amantadine though apparently act under disparate neurotransmitter system (dopaminergic path) may cause similarly pervasive increase in the aggravation of positive symptoms in schizophrenics. Thus, the question still remains that how two drugs with established different biochemical mechanisms and pharamacological properties can possibly share cross-talking or overlapping mechanisms to induce such similar effects.
It is still unclear that how these effects and the level of exacerbation in positive symptoms of schizophrenics are comparable in these different drugs.
I think that probably new comparative behavioral or psychopharmacological paradigms besides imaging (e.g. spect or PET) along with computational modelling of drug delivery and docking should be performed to address the possibility of intertwined pathway networks of these treatments (conceivably via enrichment maps).
I would be happy to see more info on this idea or alternative ones too.
Efficacy and Safety of Antidepressants Added to Antipsychotics for Schizophrenia: A Systematic Review and Meta-Analysis
Bartosz Helfer , M.Sc., Myrto T. Samara , M.D., Maximilian Huhn , M.D., Elisabeth Klupp , M.D., Claudia Leucht , M.D., Yikang Zhu , M.Med., Rolf R. Engel , Ph.D., Stefan Leucht , M.D.Published Online:10 Jun 2016https://doi.org/10.1176/appi.ajp.2016.15081035
This paper may interest you.
Thanks Beatrice for sharing this interesting met-analysis.
Although this meta-analysis did not particularly address the conceivable common ground between the underlying mechanisms of effect of antidepressants (i.e. SSRIs) and importantly certain dopamine agonists (i.e. amantadine) on the exacerbation of positive symptoms of schizophrenia, it is very engaging when we see possibly promising effects of adjunctive antidepressants and antipsychotics!
Nonetheless, again the issue here is that it seems that the results of this research also demonstrate almost the least significant effect of antidepressants on positive symptoms.
Regardless, lower risk of aggravation of psychosis and adverse effects was anticipated as the results of adjunctive medication.
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