Dosulepin

Dosulepin
Systematic (IUPAC) name
(E,Z)-3-(dibenzo[b,e]thiepin-11(6H)-ylidene)-N,N-dimethylpropan-1-amine
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy cat. C
Legal status Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability 30%
Metabolism Hepatic
Half-life 20 hours
Excretion Renal
Identifiers
CAS number 113-53-1
ATC code N06AA16
PubChem CID 13473
UNII W13O82Z7HL YesY
KEGG D07872 YesY
Chemical data
Formula C19H21NS 
Mol. mass 295.45 g/mol
 YesY(what is this?)  (verify)

Dosulepin (INN), formerly known as dothiepin (BAN), is a tricyclic antidepressant (TCA). It is sold under the brand names Prothiaden, Dothep, Thaden and Dopress. Dosulepin blocks the reuptake of serotonin and norepinephrine in the brain, thereby increasing their levels. It is believed that this action is responsible for its mood-elevating effects.

Contents

Indications

Dosulepin is relatively mild and is used for low-level anxiety, depression and similar disorders, as well as the treatment of chronic and ongoing pain disorders, particularly where insomnia and/or loss of appetite are present. It can take between two and four weeks of regular usage to become effective; it is often started at a low level and the dosage increased if this is ineffective. The drug causes drowsiness as a side-effect, and this may be used as part of the treatment, since anxiety-depressive patients may have difficulty sleeping; it can also be combined with other drugs such as temazepam. The drug is also an effective preventative for migraine.

Dosage

Adults: Initially 75 mg/day in divided doses or as a single dose at night, increasing to 150 mg/day. In certain circumstances, e.g. in hospital use or unresponsive patients, dosages up to 300 mg daily have been used.

Suggested regimens: 25 or 50 mg three times daily or, alternatively, 75 or 150 mg as a single dose at night. Should the regimen of 150 mg as a single night-time dose be adopted, it is better to give a smaller dose for the first few days.

Elderly: 50 to 75 mg daily initially. As with any antidepressant, the initial dose should be increased with caution under close supervision. Half the normal adult dose may be sufficient to produce a satisfactory clinical response.

Children: Not recommended. [1]

Side effects

The most common side effects are drowsiness and dry mouth as well as dry eyes. Other less common side effects may include:

These side effects cease when treatment ceases. Alcohol should be avoided whilst taking dosulepin as it may increase some side-effects.

Whilst dosulepin is not addictive, it should not be stopped suddenly as there is a risk of initial withdrawal symptoms which may be mistaken for some of the original indications for the drug:

  • Nausea
  • Vomiting
  • Loss of appetite
  • Headache
  • Giddiness
  • Chills
  • Insomnia
  • Anxiety

the initial withdrawal may first include symptoms of mania or hypo-mania depending on how long this TCA has been taken regularly.

Contraindications

Contra indications include:

Drug interactions

The drug can interact dangerously with vasoconstrictors and should not be taken in combination with phenylephrine or adrenaline in particular.

The sedative effects of other CNS depressants (benzodiazepines such as diazepam and lorazepam, sedative antihistamines, opiates, etc.) may be increased.

This drug should not be started within 2 weeks of stopping a monoamine oxidase inhibitor (MAOI) antidepressant, and should not be co-administered with any selective serotonin reuptake inhibitor (SSRI) antidepressant such as fluoxetine), or any medication which affects the electrical impulses to the heart (e.g. astemizole, halofantrine or terfenadine).

The drug is not recommended for use by children nor to be taken in combination with some other drugs, including herbal remedies.

Overdose

The symptoms and the treatment of an overdose are largely the same as for the other tricyclic antidepressants.

Chemistry

Dosulepin is made as follows: Dothiepin Synthesis.png

Zirkle, C. L.; 1971, U.S. Patent 3,609,167.

Dosulepin is also the dibenzothiepine analogue of doxepin, from which it differs by the replacement of the oxygen position with that of sulfur.

See also

References