Background
Description of participants
Description of interventions
Classes of antidepressants | Examples |
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Tricyclic antidepressants (TCA) | Amineptine, amitriptyline, amoxapine, butriptyline, cianopramine, clomipramine, desipramine, demexiptiline, dibenzepin, dosulepin, dothiepin, doxepin, imipramine, iprindole, lofepramine, maprotiline, melitracen, metapramine, nortriptyline, noxiptiline, opipramol, protriptyline, tianeptine, trimipramine, and quinupramine. |
Tetracyclic antidepressants (TeCAs) | Trazodone |
Monoamine oxidase inhibitors (MOI) | Isocarboxazid and phenelzine |
Selective serotonin reuptake inhibitors (SSRI) | Citalopram, dapoxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline |
Serotonin-norepinephrine reuptake inhibitors (SNRI) | Desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine |
Selective noradrenaline reuptake inhibitors (NRI) | Reboxetine |
Atypical antidepressants | Agomelatine, bupropion, mirtazapine, and nefazodone, vilazodone, and vortioxetine |
How the interventions might work
Why is it important to do this review?
Methods
Criteria for considering studies for this review
Types of studies
Types of participants
Types of interventions
Cointerventions
Outcome measures
Primary outcomes
Secondary outcomes
Exploratory outcomes
Assessment time points
Search methods for identification of studies
Electronic searches
Searching other resources
Data collection and analysis
Selection of studies
Data extraction and management
Trial characteristics
Participant characteristics
Intervention characteristics
Control characteristics
Outcomes
Notes
Assessment of risk of bias in the included trials
Bias arising from the randomisation process
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Low risk of bias. Allocation was adequately concealed, AND there are no baseline imbalances across intervention groups at baseline appear to be compatible with chance, AND an adequate (random or otherwise unpredictable) method was used to generate allocation sequence, OR there is no information about the method used to generate the allocation sequence.
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Some concerns. Allocation was adequately concealed, AND there is a problem with the method of sequence generation, OR baseline imbalances suggest a problem with the randomisation process, OR no information is provided about concealment of allocation, AND baseline imbalances across intervention groups appear to be compatible with chance, OR no information to answer any of the signalling questions,
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High risk of bias. Allocation sequence was not concealed, OR no information is provided about concealment of allocation sequence, AND baseline imbalances suggest a problem with the randomisation process.
Bias due to deviation from intended interventions
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Low risk of bias. Participants, carers, and personnel were unaware of intervention groups during the trial, OR participants, carers, or personnel were aware of intervention groups during the trial but any deviations from intended intervention reflected usual practice, OR participants, carers, or personnel were aware of intervention groups during the trial but any deviations from intended intervention were unlikely to impact on the outcome, AND no participants were analysed in the wrong intervention groups (that is, on the basis of intervention actually received rather than of randomised allocation).
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Some concerns. Participants, carers, or personnel were aware of intervention groups and there is no information on whether there were deviations from usual practice that were likely to impact on the outcome and were imbalanced between intervention groups, OR some participants were analysed in the wrong intervention groups (on the basis of intervention actually received rather than of randomised allocation) but there was little potential for a substantial impact on the estimated effect of intervention.
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High risk of bias. Participants, carers, or personnel were aware of intervention groups, and there were deviations from intended interventions that were unbalanced between the intervention groups and likely to have affected the outcome, OR some participants were analysed in the wrong intervention groups (on the basis of intervention actually received rather than of randomised allocation), and there was potential for a substantial impact on the estimated effect of intervention.
Bias due to missing outcome data
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Low risk of bias. No missing data OR non-differential missing data (similar proportion of and similar reasons for missing data in compared groups) OR evidence of robustness of effect estimate to missing data (based on adequate statistical methods for handling missing data and sensitivity analysis)
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Some concerns. An unclear degree of missing data or unclear information on proportion and reasons for missingness in compared groups AND there is no evidence that the effect estimate is robust to missing data
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High risk of bias. A high degree of missing data AND differential missing data (different proportion of or different reasons for missing data in compared groups) AND there is no evidence that the effect estimate is robust to missing data
Bias in measurement of outcomes
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Low risk of bias. The outcome assessors were unaware of the intervention received by study participants, OR the outcome assessors were aware of the intervention received by study participants, but the assessment of the outcome was unlikely to be influenced by knowledge of the intervention received.
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Some concerns. There is no information available to determine whether the assessment of the outcome is likely to be influenced by knowledge of the intervention received.
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High risk of bias. The assessment of the outcome was likely to be influenced by knowledge of the intervention received by study participants.
Bias arising from selective reporting of results
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Low risk of bias. Reported outcome data are unlikely to have been selected, on the basis of the results, from multiple outcome measurements (e.g. scales, definitions, time points) within the outcome domain, and reported outcome data are unlikely to have been selected, on the basis of the results, from multiple analyses of the data.
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Some concerns. There is insufficient information available to exclude the possibility that reported outcome data were selected, on the basis of the results, from multiple outcome measurements (e.g. scales, definitions, time points) within the outcome domain, or from multiple analyses of the data. Given that analysis intentions are often unavailable or not reported with sufficient detail, we anticipate that this will be the default judgement for most trials.
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High risk of bias. Reported outcome data are likely to have been selected, on the basis of the results, from multiple outcome measurements (e.g. scales, definitions, time points) within the outcome domain, or from multiple analyses of the data (or both).
Overall assessment of risk of bias
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Low risk of bias. The trial is judged to be at low risk of bias for all domains.
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High risk of bias. The trial is judged to be at high risk of bias or to be at some concerns in at least one domain. Our subgroup analysis will compare the intervention effect of trials at low risk of bias with trials at high risk of bias, that is one or more domains at some concern or high risk of bias.
Differences between the protocol and the review
Measurement of treatment effect
Dealing with missing data
Assessment of heterogeneity
Assessment of reporting biases
Unit of analysis issues
Data synthesis
Subgroup analysis and integration of heterogeneity
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‘Best-worst-case’ scenario. We will assume that all participants lost to follow-up in the antidepressant group survived, had no serious adverse events, had no suicides or suicide attempts, and had no non-serious adverse events, and that all those participants lost to follow-up in the control group did not survive, had a serious adverse event, died by suicide or had a suicide attempt, and had a non-serious adverse event.
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‘Worst-best-case’ scenario. We will assume that all participants lost to follow-up in the antidepressant group did not survive, had a serious adverse event, died by suicide or had a suicide attempt, and had a non-serious adverse event, and that all those participants lost to follow-up in the control group survived, had no serious adverse events, had no suicides or suicide attempts, and had no non-serious adverse events.
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Where SDs are missing and it is not possible to calculate them, we will impute SDs from trials with similar populations and low risk of bias. If we find no such trials, we will impute SDs from trials with a similar population. As the final option, we will impute the mean SD from all included trials.