Is Doxepin a Controlled Substance?
No, doxepin is not a federally controlled substance in the United States. This distinguishes it from most other pharmacologic treatments for insomnia, which are typically scheduled medications.
Regulatory Classification
- Doxepin is explicitly noted as an exception among insomnia medications because it is not a controlled substance 1, 2
- In contrast, other commonly used sleep medications carry controlled substance designations:
- Benzodiazepines (temazepam, triazolam, estazolam) are Schedule IV controlled substances 3
- Non-benzodiazepine hypnotics (zolpidem, eszopiclone, zaleplon) are Schedule IV controlled substances 3
- Modafinil and armodafinil are Schedule IV controlled substances 3
- Stimulants like methylphenidate and dextroamphetamine are Schedule II controlled substances 3
- Carisoprodol is classified as a controlled substance due to abuse potential 3
Clinical Implications of Non-Controlled Status
- The lack of controlled substance classification makes doxepin particularly advantageous for patients requiring long-term insomnia treatment without the regulatory burden and abuse concerns associated with scheduled medications 1, 2
- Low-dose doxepin (3 mg and 6 mg) received FDA approval specifically for insomnia treatment, separate from its higher-dose antidepressant formulations 2, 4
- At low doses used for insomnia, doxepin works primarily through selective histamine H₁ receptor antagonism rather than through mechanisms associated with abuse potential 4
Safety Profile Supporting Non-Controlled Status
- Studies of up to 3 months duration showed no signal for tolerance, psychomotor impairment, rebound insomnia, or discontinuation symptoms with low-dose doxepin 4
- Long-term use (5-15 years) at antidepressant doses has demonstrated safety and lack of adverse drug interactions, though this data pertains to higher doses than those used for insomnia 5
- The most common adverse effects are sedation/sleepiness and headache, occurring at rates similar to or less than placebo 4
Important Caveats
- While not a controlled substance, doxepin at higher doses (25-300 mg) used for depression is a tricyclic antidepressant with significant cardiotoxicity in overdose 6
- The non-controlled status applies to all doses, but the safety profile and clinical use differ substantially between low-dose (1-6 mg) hypnotic formulations and higher-dose antidepressant formulations 2, 6