None of the antipsychotics is safe (neither first or second generation). However, although cases of NMS induced by clozapine or quetiapine were published, I consider these two (and clozapine in particular) as more safe than others.

In my view clozapine and quit alpine is relatively safer,I am also not aware of many reports about amsulipride and tiapride

Dear ul rich frick,

Apologies for using word safe and not safer or rather precisely relatively safer,my experience is from about 30 patients of Varying degrees of NMS from last 10 years all of whom were on typical antipsychotics most of then on haloperidol oral or injectable which are still prescribed very commonly particularly by non psychiatrists in my part of world all of them were re challenged with atypical antipsychotics most of them with clozapine and quiet alpine and none of them had any relapse with NMS Or NMS like symptoms ,but one patient with resperidone relapsed .I am also aware of very few case reports with with amisulipride I think one or two and same about tiapride .and tiapride case is a special NMS case of have double NMS one with tiapride and then with smallest reported doses of haloperidol reported , perhaps in accordance with your point of sub group and what I understand as specific genetic polymorphism .

My apologies again for being too clinical without detail , but question to me looked clinical rather research directed as all psychiatrists are aware that NMS has been reported with everything and anything they use SSRI, LITHIUM etc etc.

Dear Prof Frick , thank you very much for your advice. I am aware about the clinical data and as you mentioned , none is safe. I was looking for more personal experiences of clinicians and anything new being done.

Dear Colleagues,

I think that predicting NMS recurrence is complicated due to the fact that apart from treatment related factors (i.e. use of first generation antipsychotics in high doses) and individual factors (e.g. young, male patient), there are temporary factors that may contribute to the occurrence of NMS, e.g. dehydration, infection with raised temperature or cardio-vascular events (e.g. TIA). All these may "facilitate" the development of NMS in any patient and will significantly contribute to his/her individual risk. I think that in many cases this "non-constant" factors may increase the risk more that well defined factors, thus making predicting NMS risk very difficult.

I agree with some authors. Clozapine seems safer, though it could still cause NMS

Clozapine is the least likely to cause NMS but should be given with caution due to its other potentially lethal side effects (Agranularcytosis) What needs to be done in all patients who have been severely adversely affected by neuroleptics is a full liver function test and a test for the P450 cytochromes involved in the individual drug metabolism. Concomitant prescribing of drugs that counteract each others metabolism is a cause of NMS and the failure to understand pharmacodynamics by many prescribers is at fault. As many as 7% of the population cannot metabolise these drugs, yet when they fail to respond to the treatment it is often the case that the prescriber will titrate up the dose without checking first whether the patient is a poor or non-metaboliser

Interesting question leading to interesting reading- thank you for asking it

As in Barry Turner's answer, many sources emphasize that there are a multitude of risk factors some of which may change, for example, alcohol use or concurrent other counteracting medications. This also means that rechallenge may be an option if inpatient observation is plausible.

Given the variety ( and lengthy list of risk factors) no single "safe" answer is possible but would be accordingly varied for each  patient.

You may wish to read:

.Neuroleptic malignant syndrome: Answers to 6 tough questionswww.nmsis.org/content.asp?type=publications.../nms...‎ 

Handbook of Consultation-Liaison Psychiatry

https://books.google.com/books?isbn=3319110055

Hoyle Leigh, Jon Streltzer - ‎2014 - Medical

... (33% increased risk) are other factors found to increase the risk for NMS ...

NMS Review for the USMLE Clinical Skills Exam -

https://books.google.com/books?isbn=0781766931

Erich A. Arias, Nelly Amador - ‎2008 - Medical

Other important risk factors ...

Regards