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December 23, 2004
Paroxetine and negative symptoms?
Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: a double-blind placebo-controlled study
M. C. Jockers-Scherübl, A. Bauer, F. Godemann, F. M. Reischies, F. Selig and P. Schlattmann
International Clinical Psychopharmacology 2005, 20:27–31
Schizophrenia is often discussed in terms of three types of symptoms: Positive symptoms, negative symptoms and cognitive symptoms. The positive symptoms are the most widely discussed and include delusions, hallucinations (most commonly auditory or voices), paranoia and other bizarre thinking. Negative symptoms include blunted affect (affect meaning the way that emotion is expressed), social withdrawal, apathy and difficulty with relating to other people. Cognitive symptoms reflect the way that many people with schizophrenia have problems with working memory and/or have other deficits in their ability to think.
Antipsychotic medications are primarily agents that work on the positive symptoms. They help to take away voices and diminish paranoid feelings and often will make the feelings of having delusional thoughts less concerning. However, they rarely help with negative symptoms. Clozapine is the only medicine that has ever been shown to help with negative symptoms and it does so only modestly. There are many theories about the genesis of negative symptoms and many believe that they represent a different dysfunction in the brain than the cognitive symptoms. That theory would perhaps explain why medicines that treat positive symptoms are ineffective on negative symptoms. However, that alternate pathway, while the source of many theories, is largely unknown.
One feature of negative symptoms that has interested the research community is that it shares many features with major depression. The social isolation, lack of motivation and withdrawn emotions are similar to symptoms one might experience in a depression. This study looks at using an SSRI (selective serotonin reuptake inhibitor) medication, paroxetine (Paxil) to see if it might help with negative symptoms.
The authors designed a study that utilized “randomized, placebo-controlled, double blind” technique. Randomized means that every subject was equally likely to get placebo (dummy pill) or the experimental agent (paroxetine). Placebo controlled means that they were using a placebo, an inert pill, to compare with an active treatment, paroxetine. This helps to determine if any benefit seen may be from the “placebo effect” which is where some patients (often up to 30% or more) can benefit from taking the inert treatment. Double blind means that the researchers and the patients did not know what they were on until after the data was collected, thereby decreasing the risk that someone might unconsciously report better results for the group they wanted to do better (typically the experimental group.) The researchers limited their study to patients with a stable recent history (no antipsychotic changes in the last 6 months) and they could not have any alcohol/drug problems, had to have minimal positive symptoms, and could not have any current evidence of depression (based on 2 depression rating scales.) This leaves a very select group of patients to study, but one that would hopefully give results that would not be as open to questions of confounding variables.
The authors found that adding paroxetine helped with 3 areas of negative symptoms. There were modest effects seen in ratings of affective blunting, impaired abstract thinking and spontaneous speech and spontaneity. The paroxetine was no different from placebo in other measures of negative symptoms (emotional withdrawal, poor rapport, passive social withdrawal and stereotyped thinking.) The authors stated that there were few side effects reported, however there were 3 patients who dropped out from the paroxetine group and one patient from the placebo group with side effects (out of 29 patients that started the study.)
Ultimately, the benefit from the paroxetine is modest at best. The side effects however are generally minimal (though not always.) It is unknown still why paroxetine might be influential though there are theories ranging from influence on the neurotransmitter serotonin to perhaps ways that paroxetine might subtly influence the release of dopamine in specific parts of the brain. Dopamine is thought to have an influence in positive symptoms when it is too high in some parts of the brain, however it is a neurotransmitter that is also associated with pleasure and reward centers in the brain and perhaps the paroxetine has an effect more in those regions than in the areas associated with positive symptoms. This study does not provide the evidence needed to say that everyone should be on paroxetine if they have negative symptoms. It does suggest that it might be a safe medication to try if that is a problem however and that it might help some people.
Conflict of interest: The study was supported as an investigator initiated trial by GlaxoSmithKline (maker of paroxetine (Paxil).Posted by Jacob at December 23, 2004 06:44 PM | TrackBack