Clomipramine

ID: clomipramine

Aliases: Anafranil

Type: compound

Route/form: oral

Status: approved

Evidence level: approved / labelled

Best data tier: approved label + human controlled/review

Support scope: human, review/regulatory

Source types: evidence_report, human_association_and_preclinical, human_rct, label, meta_analysis

Linked sources: 6

Broad outcomes: Brain / mood / sleep

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• serotonin transporter inhibitor
• tricyclic antidepressant

Optimization domains

• OCD
• depression
• anxiety

Research basis

• Clomipramine is a potent serotonergic TCA with strong OCD/panic/depression evidence and belongs in the repository because communities discuss it when SSRIs feel too mild.
• Head-to-head and meta-analytic evidence supports efficacy, but also helps explain why tolerability is the tradeoff.
• Optimization framing should treat it as a high-burden psychiatric drug, not a casual anxiolytic.

Limits, risks, and missing evidence

• Anticholinergic burden, orthostasis, weight/sexual effects, QT/conduction effects, seizure threshold, overdose toxicity, and interaction load are much heavier than typical SSRI tradeoffs.
• Like other strongly anticholinergic drugs, chronic cumulative exposure is linked observationally with cognitive/dementia, delirium, and fall concerns in older adults; this should be treated as a class-level risk signal, not proof that clomipramine causes dementia in every user.
• Stacking with sertraline, trazodone, stimulants, antihistamines, or MAOIs can be dangerous.
• Greater potency is not automatically better if side effects reduce sleep, adherence, or cardiovascular safety.

Risk flags

• approved drug
• serotonergic
• anticholinergic
• cumulative anticholinergic burden
• older adult high risk
• dementia association observational
• sedating
• qt conduction risk
• overdose toxicity
• interaction risk

Linked papers, labels, and reviews

1. FDA label: Anafranil clomipramine hydrochloride
   label / fda_clomipramine_label
   Official label.
2. Superiority of clomipramine over imipramine in the treatment of panic disorder: a placebo-controlled trial
   human_rct / pubmed_clomipramine_panic_1992
   Panic-disorder RCT; relevant to anxiety/panic discussions, while label risks and tolerability still dominate practical use.
3. Influence of study characteristics, methodological rigour and publication bias on efficacy of pharmacotherapy in obsessive-compulsive disorder
   meta_analysis / pmc_ocd_pharmacotherapy_meta_2022
   Meta-analysis of randomized placebo-controlled OCD pharmacotherapy trials including clomipramine; useful indication-level context.
4. A double-blind study of the efficacy and safety of sertraline and clomipramine in severe major depression
   human_rct / pubmed_sertraline_clomipramine_depression_2000
   Head-to-head tolerability/efficacy comparison useful for explaining why clomipramine potency comes with a heavier adverse-effect burden.
5. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults
   evidence_report / pubmed_ags_beers_criteria_2023
   Geriatric prescribing criteria covering strongly anticholinergic drugs, including first-generation antihistamines and selected antidepressants; useful for older-adult delirium, falls, cumulative anticholinergic burden, and dementia-risk framing.
6. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study
   human_association_and_preclinical / pubmed_anticholinergic_dementia_coupland_2019
   Large nested case-control study; supports cumulative anticholinergic burden as a dementia-risk signal while requiring class-specific and confounding-aware interpretation.