Hi. The American Journal of Psychiatry publishes an interesting review concerning this topic in the issue of May. It may be useful for answer your question.

This is the reference:

The Long-Term Effects of Antipsychotic Medication on Clinical Course in Schizophrenia.

Donald C., Goff, M.D., Peter Falkai, M.D., Ph.D., W. Wolfgang Fleischhacker, M.D., Ragy R. Girgis, M.D., Rene M. Kahn, M.D., Ph.D., Hiroyuki Uchida, M.D., Ph.D., Jingping Zhao, M.D., Ph.D., Jeffrey A. Lieberman, M.D.

Am J Psychiatry. 2017 May 5:appiajp201716091016. doi: 10.1176/appi.ajp.2017.16091016.

Best regards.

Roberto

Hi Joao,

I agree with my colleague mr.Miyuru  that obvious effects such as metabolic, neurological or increased cardiovascular risk are well documented in the literature.

However in my everyday clinical practice  I found that long term intake of antipsychotics surely have a negative effect on cognitive abilities. This topic would definitely deserve far-reaching studies in order to develop a targeted pharmacological research.

Best regards

Francesco

One area that has not been fully investigated in the literature is the connection between the aberrant behavior (most often the reason for prescribing antipsychotics in children, adolescent, young adults) and isolated epileptiform discharges (IEDs). Antipsychotics, by their nature, lower seizure threshold and increase IEDs. IEDs identified in the temporal or occipital lobes can account for psychotic events and IEDs anywhere can be linked to aggression. Therefore, the use of antipsychotics in those with IED's (32% in those with ADHD and 36.4% in those with autism; see my articles listed in pubmed) could account for many iatrogenic side-effects. This is particularly true during puberty.  

Do not forget that both treated and untreated chronic psychotic illness is associated with executive functioning deficits and other cognitive deficits. Some impairment is from the brain disease and some impairment may be from medications. Prior to the existence of antipsychotics, schizophrenia was referred to as dementia precox (premature dementia) because of the severe cognitive impairment that progresses as the disease progresses. It is a fallacy to think this only began to occur when we finally had some symptomatic treatment available. Clozapine is the only antipsychotic I am aware of that has data supporting cognitive improvement.

The atypical antipsychotics are generally not related to each other chemically and so though we often talk about them as if they have the same risks and benfits it is not true. Ziprasidone does not have metabolic side effects while olanzapine often (though not always) does. Risperidone has significant effects on prolactin while other atypicals and typicals generally do not have this.

Mr Swatzyna makes some points above but they are entirely speculative. This does not make his hypothesis true or false. I am just pointing out this the association he mentions does not prove causality.

Dear All

Many thanks for all the replies and I am sorry for the delay in getting back to you. I think all of you mentioned extremely important points which need further investigation. 

However, the main point I was trying to make was related to dopamine receptor sensitivity follwoing long-term antypsychotic intake and the "withdrawal" effects of stopping the drugs. 

Mrs Nash point that prior to the existence of neuroleptics the cognitive impairments in "schizophrenics" were already observed is true. However, it is arguable (at he very least) that the cognitive impairments were due to the "ilness" progression and not to the inhuman and brutal treatment conditions of the time. 

The Open Dialogue project in Finland is a good example that shows 83% remission rates in "schizophrenia" with little or no antypsychotic use. Instead, they use a humanistic model, rooted in psychotherapeutic and systemic theory. 

It makes one think what is really going on...