Schizophrenia is considered a chronic long-term debilitating condition, affecting about 1% of the population. There has been considerable debate about which of the anti-psychotic medications are the best treatments. The debate has usually been structured around typical (older) and atypical (newer) anti-psychotic medications. The revised NICE guidelines (2009) moved towards a more neutral stance between atypical (newer drugs) and typical (older drugs) anti-psychotics.
This aimed to compare fifteen antipsychotic drugs across seven domains including effectiveness/efficacy (symptom reduction PSYRATS or BPRS), and all cause discontinuation, side effects including Extrapyramidal Side Effects (EPSE), weight gain, prolactin increase, QTc prolongation, and sedation. The authors conducted a Bayesian-framework, multiple treatment meta-analysis.
- 212 trials containing 43,209 participants were identified, 144 (68%) had been conducted by the pharmaceutical industry.
- All drugs included in the analysis fared better than placebo.
- There were high rates of withdrawal across all the studies at about 35%.
- No one drug was best across all the domains – see summary table of best/worst performers across the domains.
- Five atypical anti-psychotics had significantly more EPSE than placebo.
- Efficacy (symptom change) – the best performers were Clozapine, Amisulpride & Olanzapine, the worst performers were Asenapine, Lurasidone & Iloperidone.
- All cause discontinuation – the best performers were Amisulpride, Olanzapine & Clozapine, the worst performers were Lurasidone, Sertindole & Haloperidol.
- EPSE – the best performers were Clozapine, Sertindole & Olanzapine, the worst performers Chlorpromazine, Zotepine & Haloperidol.
- Weight gain – the best performers were Haloperidol, Ziprasidone & Lurasidone, the worst performers Clozapine, Zotepine & Olanzapine.
- Prolactin increase* – the best performers were Aripiprazole, Quetiapine & Asenapine, the worst performers were Haloperidol, Risperidone & Paliperidone.
- QTc prolongation** – the best performers were Lurasidone, Aripirazole & Paliperidone, the worst performers were Ziprasidone, Amisulpride & Sertindole.
- Sedation – the best performers were Amisulpride, Paliperidone & Sertindole, the worst performers were Chlorpromazine, Zotepine & Clozapine.
*Not applicable Amisulpride Clozapine Zotepine, **Not applicable Clozapine Chlopromazine Zotepine
‘Results for our primary outcome challenge the dogma that the efficiency of all antipsychotic drugs is the same.’
‘Antipsychotics differed substantially in side-effects and small but robust differences were seen in efficacy. Our findings challenge the straightforward classification of antipsychotics into first-generation and second-generation groupings. Rather, hierarchies in the different domains should help clinicians to adapt the choice of antipsychotic drug to the needs of individual patients.’
It’s interesting to note the differences between the anti-psychotics which might help to challenge some clinician’s beliefs that certain drugs (atypicals) are better than others despite evidence to the contrary (see here). There is clearly a need for a more individualised approach to prescribing which involves negotiation and cost-benefit analysis for each individual service user/patient taking into account the potential side effect profiles and benefits of each drug. The authors suggested that cost appears to becoming a less issue, although atypical anti-psychotics are more expensive especially when new to the market.
Dosing still appears key, although this is not really clear from this review, often trials which compare atypicals with typical anti-psychotics use typical doses above the 7.5 mg Haloperidol or less recommended for treatment of acute psychosis (see here). Some side effects are dose dependent. Further analysis needs to factor this in.
There were some limitations with the review some drugs are not currently used in the UK, others have a good evidence base underpinning them but not included in the analysis, for example, sulpiride and perphenazine. There were some potential problems with the analysis, for example, the use of all cause discontinuation as a proxy measure of acceptability.
Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel R, Geddes J, Kissling W, Stapf M, Lassig B, Salanti G, Davis J (2013) Comparative efficacy and tolerability of 15 anti-psychotic drugs in schizophrenia: a multiple-treatments meta-analysis. The Lancet, Early Online Publication, 27 June 2013
my been stable for about 3 to 4 years on a combination of Clozopine, 200mg of Largactil and 60 mg of diazepam a day, how he stays awake and functions I will never know but function he does
Systematic review: which anti-psychotic medication is the best? http://t.co/EEneNQEHq1 via @sharethis
@Mental_Elf Interesting for populations, but doesn’t it boil down to individual tolerability and efficacy? So easy if all were the same…
great post! I sincerely hope that people will refrain from lumping distinct drugs into these arbitrary categories of typical vs atypical APs. incidentally, did the review subdivide symptoms, i.e. with respect to positive vs. negative symptoms? while it’s widely claimed that atypical APs factually improve negative symptoms, i have this notion that they only mess you up less than typicals…
Systematic review: which anti-psychotic medication is the best?: Schizophrenia is considered a chronic long-t… http://t.co/WvyQ4bryWd
great to hear!
This review found significant differences between antipsychotics in effectiveness and side effects: http://t.co/WhB75SaFda
@Mental_Elf Useful reference.
resperidin for me
Useful summary: Systematic review: which anti-psychotic medication is the best? http://t.co/8AKXo60wCA via @sharethis
Quetiapine works for me
In overall symptom change, the best performers were clozapine, amisulpride and olanzapine: http://t.co/WhB75SaFda
@Mental_Elf Was just speaking about Amisulpride & Clozapine with a psychiatrist an hour ago. Studies in Portugal claim Amisulpride efficacy
@Mental_Elf clozapine certainly if client is fully compliant but a nightmare if not !!
@Mental_Elf interesting article, but I feel flawed in that such a high percentage of trials came from the pharmaceutical industry
@Mental_Elf independent trials (from what I know) show that most or all of the atypicals induce worse side-effects and are less efficacious
Which anti-psychotic medication is the best? – The Mental Elf http://t.co/7GZKoWP9aX
Don’t miss this great blog on #antipsychotics from mental health nurse and researcher @JohnBaker_UoM http://t.co/XkODBBzeyN
You have to read this : Systematic review: which anti-psychotic medication is the best? http://t.co/KvesNTlTtB via @JohnBaker_UoM
RT @Mental_Elf: Many studies of antispychotic medications suffer a high drop-out rate: http://t.co/WhB75SaFda
Systematic review of the effects of different antipsychotic medications, combining data from over 212 studies: http://t.co/WhB75SaFda
@Mental_Elf Good number of sensitivity analyses! Went straight to check for industry sponsorship analysis…
Which anti-psychotic medication is the best? – The Mental Elf http://t.co/mtw1hjPvoD Worth reading
Interesting@Mental_Elf:Systematic review of different antipsychotic medications,combining data from over 212 studies: http://t.co/H8wiaAgkFC
Mental Elf: Systematic review: which anti-psychotic medication is the best? http://t.co/l9XH4b5KOc
From @Mental_Elf Systematic review: which anti-psychotic medication is the best? http://t.co/t8z5jJYsaT
Runners up: @dr_know http://t.co/XCGr9AMb5v @markhoro http://t.co/becHU8f8z1 @JohnBaker_UoM http://t.co/XkODBBzeyN
@Mental_Elf well. This is ON. ;)
Nice blog on this Lancet paper from Prof Simon Hatcher here: http://uottawapsychiatry.blogspot.co.uk/2013/08/comparative-efficacy-and-tolerability.html
Systematic review: which anti-psychotic medication is the best? http://t.co/6VrFG3cuzW via @sharethis #mhuk #ukmh
New study shows different types of antipsychotics have substantially different efficacy & side effects http://t.co/DMrD7eYaKj #schizophrenia
Interesting view of antipsychotics. I agree the dose given and if you are on other medication the cumulative effect of that is not clearly explained in research studies. Also gender differences not included?
Systematic review: which antipsychotic medication is the best? http://t.co/Z9aNi0f529 #SchizophreniaAwarenessWeek
Systematic review: which antipsychotic medication is the best? via @Mental_Elf | http://t.co/idCL4UyGOW
[…] are the mainstay of treatment, but they have low success rates (~60%), disabling adverse effects, damaging impact on physical health, and poor patient outcomes following ineffective treatment are […]
[…] It is unclear from the paper whether all side effects were considered or just specific ones. There is some discussion about extra-pyramidal side effects associated with older antipsychotic medications, and weight gain associated with the newer antipsychotics was also raised. However, there’s nothing on sexual dysfunction or metabolic syndrome, which is an omission. If we are to enable a clear choice between different antipsychotic treatments (not considered in this paper), we will need a detailed understanding of the risks and benefits of each drug, as discussed in this previous blog. […]
[…] and safety of both first and second generation antipsychotics. A key meta-analysis from 2013 (blogged about here) has suggested that clozapine is the most effective second generation antipsychotic and quetiapine […]
Its interesting that there is no mention of what (if any) “anti psychotic” impact these drugs had on the people taking them (aside presumably, from the inevitable sedation), nor anything about how they effected their quality of life…
My son is on haldon and says it is giving him bad blurry vision do you know what other med works better for schizophrenia
My brother is suffering from both schizophrenia and bipolarity. Would you recommend some drug which can help?
What are the best treatment options for a patient with a history of neutropenia? Was on olanzapine and aripiprazole but d/c due to neutropenia
I am a Christian and currently on Clozapine. The clozapine has been great for me. While I still hear voices the clozapine makes sure I am not listening to them at night. My faith helps me to rationalise the fact that I live with these voices. For me the psychiatric profession falls short when it does not consider the possibility that there may also be a spiritual contribution to the individuals condition.
I am feeling like I can’t and don’t want to do anything on Arippiroole 400 mg a month. Scared to go out sometimes. Please is there a antipychotic drug which doesn’t effect you in this way please?
Wil fix you 👍
As the article says. Individualized treatment is required. One shoe does not fit all! So far I have had good results with Seroquel, risperidone, Paliperidone, and Arapiprazole. I take a med range dose of Arapiprazole and do not think it is right for me. However, finding the right psychiatrist and living a full and complete life (strive to be great) for me is like finding hens teeth.
By “all cause discontinuation”, is it meant that you are in the end cured of your illness, as in curing potential, or something else? Please let me know, I am unsure but currently taking antipsychotics.