# Screening codebook: which adverse-event groups compare an antidepressant with placebo

Each record is a randomized, parallel-group or factorial trial on ClinicalTrials.gov with posted results, found by searching interventions for an antidepressant. You see its titles, conditions, phases, masking, eligible ages, arms with their descriptions and interventions, and the groups its adverse-event tables are reported by (`ae_groups`), with no counts. Decide, for each trial, which adverse-event groups form clean comparisons of an antidepressant against placebo, and classify the trial's design and indication.

## What counts

**An antidepressant group** is an adverse-event group whose participants were randomized to receive one of these drugs, at any dose or route: sertraline, fluoxetine, paroxetine, citalopram, escitalopram, fluvoxamine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, levomilnacipran, vortioxetine, vilazodone, bupropion, mirtazapine, mianserin, trazodone, nefazodone, agomelatine, esketamine, zuranolone, brexanolone, gepirone, the combination dextromethorphan–bupropion (approved as an antidepressant), a tricyclic or tetracyclic antidepressant (amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, doxepin, trimipramine, protriptyline, maprotiline, amoxapine), or a monoamine oxidase inhibitor used as an antidepressant (phenelzine, tranylcypromine, isocarboxazid, transdermal selegiline, moclobemide), or another drug the record describes as an antidepressant (name it in `note`). Racemic ketamine, psychedelics, antipsychotics, benzodiazepines, and drugs given only as an anaesthetic are not antidepressants here. Several doses or several antidepressants may be pooled into one comparison.

**A placebo group** is an adverse-event group whose participants were randomized to placebo for that antidepressant (or to no added drug in a double-blind design), with everything else the same as the antidepressant group: the same background therapy, the same co-interventions, the same period. Background therapy may itself be an antidepressant, as long as both sides receive it (for example esketamine with an oral antidepressant against placebo with the same oral antidepressant).

**A comparison** is a set of antidepressant groups and a set of placebo groups that differ only in the antidepressant. A factorial trial, or one with several background regimens reported in separate groups, may have several comparisons, one per background. Each adverse-event group belongs to at most one comparison.

**A combination product** is an antidepressant given in one product with another active drug the placebo group doesn't receive: naltrexone–bupropion, olanzapine–fluoxetine, or any other. Such a group may form a comparison, but mark that comparison with `"combination": "<the other drug>"`, so the analysis can keep it apart. Dextromethorphan–bupropion is not a combination here: the product is the antidepressant.

## What doesn't count

Leave a group out of every comparison when:

- **It combines the antidepressant with another active drug that isn't one product**, and the comparator doesn't get that drug (for example sertraline plus a psychotherapy the placebo group doesn't get, or an antidepressant plus an investigational drug against placebo alone).
- **It gets an active comparator**, even under a double dummy, unless that comparator is itself an antidepressant (a three-arm trial of a new antidepressant, duloxetine and placebo gives one comparison: both antidepressant groups against placebo).
- **It gets a drug that isn't an antidepressant** (an investigational drug of another class, an antipsychotic, a benzodiazepine).
- **It is open-label "no treatment" or usual care** with no placebo.
- **It isn't a randomized arm over the randomized period**: an open-label run-in or lead-in, an open-label extension, a group of everyone in the trial, a period after placebo participants switched to the drug, or a group that mixes exposures.
- **The antidepressant is background therapy in every arm** and the trial tests something else.

When no clean comparison remains, the trial is ineligible: set `eligible` to false and give the reason.

## Design

- `acute`: participants were randomized at the start to the antidepressant or placebo. Prevention trials in people without the condition, and add-on trials randomized at the start, are acute.
- `randomized_withdrawal`: participants first received the antidepressant (open-label or single-blind), and those who responded or stabilized were then randomized to continue it or switch to placebo; the comparison is from the randomized phase. Relapse-prevention and maintenance trials built this way belong here.
- `other`: any other design; explain in `note`.

## Indication

What the trial treats or prevents, from its conditions and titles:

- `depressive`: a depressive disorder or depressive symptoms as the target: major depressive disorder, persistent depressive disorder, treatment-resistant depression, postpartum or perinatal depression, bipolar depression, depression with a medical illness, prevention of depression.
- `other_psychiatric`: any other mental disorder as DSM-5 counts them: anxiety, trauma- and stressor-related, obsessive-compulsive, neurodevelopmental (ADHD, autism), eating, substance use (including tobacco and smoking cessation), sleep–wake, schizophrenia spectrum, bipolar disorder outside a depressive episode, and behavioural symptoms of neurocognitive disorders.
- `non_psychiatric`: anything else: pain conditions, menopausal vasomotor symptoms, obesity, stroke recovery, irritable bowel syndrome, urinary incontinence, infections, cancer, sexual dysfunction, and the like.

When a trial targets more than one, give the main one and say so in `indication_note`.

## Output

One JSON object per trial, in the order given, as a JSON array written to the file named in your task:

```json
{
  "nct": "NCT01234567",
  "eligible": true,
  "exclusion_reason": null,
  "comparisons": [
    {"antidepressant_groups": ["EG000", "EG001"], "placebo_groups": ["EG002"], "molecules": ["vortioxetine", "duloxetine"], "background": "none", "combination": null}
  ],
  "design": "acute",
  "indication": "depressive",
  "indication_note": "",
  "note": ""
}
```

- `exclusion_reason` (when `eligible` is false), one of: `no_antidepressant_group`, `no_placebo_group`, `combined_with_other_active`, `active_comparator_only`, `background_differs`, `groups_not_randomized_arms`, `antidepressant_is_background`, `other` (explain in `note`).
- `molecules`: the antidepressants in that comparison's antidepressant groups, lower case, as named above (`dextromethorphan-bupropion` for the combination).
- `background`: a few words on what both sides of the comparison also received, or `"none"`.
- `combination`: `null`, or the other active drug of a combination product, lower case.
- For an ineligible trial, still give `design` and `indication` as best you can.
- `note`: anything a second reader would need to follow your decision, especially when a group's identity or the background is unclear. Keep it short.

Decide from the record alone. Don't look up results, publications, or other records, and don't open any other files.