BACKGROUND: Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is unclear. We aimed to compare risks and benefits of reduced versus standard doses of antipsychotics.
METHODS: We searched Embase, Medline, PsycINFO, and the Cochrane Library from database inception until June 17, 2020, for randomised trials in adults with schizophrenia or schizoaffective disorder lasting at least 24 weeks, including individuals clinically stable at baseline, and comparing at least two doses of the same antipsychotic, excluding trials in first-episode psychosis or treatment-resistant schizophrenia. We compared low-dose (within 50-99% of the lower limit of the standard dose) and very-low dose (less than 50% of the lower limit) with standard dose, defined as doses higher than the lower limit of the treatment dose recommended by the International Consensus Study. Data from published reports on number of participants, treatment, sex, age, number of events, and changes in psychopathology scores were extracted independently by at least two authors. Investigators or sponsors were contacted by email to obtain missing information regarding outcomes. Co-primary outcomes were relapse and all-cause discontinuation. Study-level data were meta-analysed using random-effects models, calculating risk ratios (RRs) for dichotomous data, and Hedges’ g for continuous data. The protocol was registered with OSF registries.
FINDINGS: 7853 references were identified in the database search and one additional reference from a manual review of relevant studies. 5744 abstracts were assessed for eligibility, and 101 references were assessed for full-text review. Of these, 79 were excluded for a variety of reasons, resulting in 22 studies being included in the meta-analysis, reporting on 24 trials and 3282 individuals. Study participants had a median age of 38 years (IQR 36-40) with 2166 (65·9%) males and 1116 (34·0%) females. Compared with standard dose, low dose increased the risk of relapse by 44% (16 trials, 1920 participants; RR 1·44, 95% CI 1·10-1·87; p=0·0076; I2=46%) and the risk of all-cause discontinuation by 12% (16 trials, 1932 participants; RR 1·12, 1·03-1·22; p=0·0085; I2=0%). Very low dose increased the risk of relapse by 72% (13 trials, 2058 participants; RR 1·72, 95% CI 1·29-2·29; p=0·0002; I2=70%) and all-cause discontinuation by 31% (11 trials, 1866 participants; RR 1·31, 1·11-1·54; p=0·0011; I2=63%). Compared with low dose, very low dose did not significantly increase the risk of relapse (five trials, 686 participants; RR 1·31, 95% CI 0·96-1·79; p=0·092; I2=51%) or all-cause discontinuation (five trials 686 participants; RR 1·11, 95% CI 0·95-1·30; p=0·18; I2=43%). Subgroup analyses comparing double-blind versus open-label studies, first-generation versus second-generation antipsychotics, and oral versus long-acting injectable antipsychotics were consistent with the overall results. Most studies were classified as having some concerns in the risk of bias assessment, which was mainly caused by absence of publicly available study registrations.
INTERPRETATION: During maintenance treatment in multi-episode schizophrenia, antipsychotic doses should probably not be reduced below the standard dose range recommended for acute stabilisation, because reducing the dose further is associated with an increased risk of both relapse and all-cause discontinuation.
Just pulling out the results, as that is a lot of text.
did they mention the exact dosage used? like what mass of medicine did they trial it with?
It was a lot of medicines. This is a meta analysis of many trials.
24 trials and 3282 individuals
They also included oral and injectable and 1st and second generation
Subgroup analyses comparing double-blind versus open-label studies, first-generation versus second-generation antipsychotics, and oral versus long-acting injectable antipsychotics were consistent with the overall results.
What they mean by low dose is 50 to 99% of the lowest standard dose as given by the manufacturer.
We compared low-dose (within 50-99% of the lower limit of the standard dose)
What they mean for very low dose is less than 50% of the lowest standard dose.
very-low dose (less than 50% of the lower limit)
And for standard dose, a dose higher than the lower limit
standard dose, defined as doses higher than the lower limit of the treatment dose recommended by the International Consensus Study.
Like if a particular medication had a 2mg to 8mg range, and if you were taking 2mg+ that would be considered standard dose per this study (I think). And below that dose would be low or very low. That is my interpretation and of course every medication is going to have a different number of milligrams that is reccomended for the standard dose. I would ask your doctor, they would know what the standard dose is for your medication.
I think the main take away for this is that it’s probably risky to go under the minimum reccomended dose. It looks like when they did the studies for these various drugs they probably correctly determined the minimum effective doses pretty well.
Thanks but from the last paragraph you quoted, wouldn’t standard dose be like 4 mg for a medicine with 2-8 mg range? And low dose be like 2 mg? So low dose is 1mg and it prevented relapses even though they went below the recommended amount?
I don’t think so, because they’ve defined the standard dose as a dose higher than the lower limit. If your range for a particular med is 2-8mg, then 4mg would still qualify as a standard dose, but so would anything 2-8mg.
Although the way it is wriiten is confusing, they describe the next tier down (low dose) as 50-99% of the lowest standard dose, not 100% of the lowest standard dose. So anything in that 2-8mg range would be “standard.”
If the range is 2-8mg, 1mg would be 50% of the lower limit of the standard dose, and in the study that increased relapse risk by 44% compared to the standard dose.