Dosulepin formerly known as dothiepin (BAN

British Approved Name

A British Approved Name is the official non-proprietary or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia...

), is a tricyclic antidepressant

Tricyclic antidepressant

Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...

 (TCA). It is sold under the brand names Prothiaden, Dothep, Thaden and Dopress. Dosulepin blocks the reuptake

Reuptake

Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....

 of serotonin

Serotonin

Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 and norepinephrine

Norepinephrine

Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 in the brain, thereby increasing their levels. It is believed that this action is responsible for its mood-elevating effects.

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

Temazepam

Temazepam is an intermediate-acting 3-hydroxy benzodiazepine. It is mostly prescribed for the short-term treatment of sleeplessness in patients who have difficulty maintaining sleep...

. The drug is also an effective preventative for migraine

Migraine

Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...

.

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.

Side effects

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

• Dizziness
  Dizziness
  Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
  
  
• Blurred vision
  Blurred vision
  -Causes:There are many causes of blurred vision:* Use of atropine or other anticholinergics* Presbyopia -- Difficulty focusing on objects that are close. The elderly are common victims....
  
  
• Tachycardia
  Tachycardia
  Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
  
  
• Urinary retention
  Urinary retention
  Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
  
  
• Tremor
  Tremor
  A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
  
  s, especially of the hands
• Blood disorders
• Hypotension
  Hypotension
  In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
  
  
• Sexual dysfunction
  Sexual dysfunction
  Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
  
  
• Sweating
  Sweating
  Perspiration is the production of a fluid consisting primarily of water as well as various dissolved solids , that is excreted by the sweat glands in the skin of mammals...
  
  
• Increased sensitivity to sunlight and increased vulnerability to sunburn

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:

• Certain conditions of the heart, mainly those affecting the electrical impulses to the heart muscle, particularly arrhythmia or recent heart attack
  Myocardial infarction
  Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
  
  
• Liver disease
  Liver disease
  Liver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
  
   or thyroid disease
  Thyroid disease
  -Hyper- and hypofunction:Imbalance in production of thyroid hormones arises from dysfunction of the thyroid gland itself, the pituitary gland, which produces thyroid-stimulating hormone , or the hypothalamus, which regulates the pituitary gland via thyrotropin-releasing hormone . Concentrations of...
  
  
• Epilepsy
  Epilepsy
  Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
  
  , phaeochromocytoma, glaucoma
  Glaucoma
  Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
  
   or diabetes
• Hypotension
  Hypotension
  In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
  
  , vulnerability to dizziness or fainting
• History of urinary retention
  Urinary retention
  Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
  
   or porphyria
  Porphyria
  Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway . They are broadly classified as acute porphyrias and cutaneous porphyrias, based on the site of the overproduction and accumulation of the porphyrins...
  
  

Drug interactions

The drug can interact dangerously with vasoconstrictors and should not be taken in combination with phenylephrine

Phenylephrine

Phenylephrine is a selective α1-adrenergic receptor agonist used primarily as a decongestant, as an agent to dilate the pupil, and to increase blood pressure...

 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

Monoamine oxidase inhibitor

Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....

 (MAOI) antidepressant, and should not be co-administered with any selective serotonin reuptake inhibitor (SSRI) antidepressant such as fluoxetine

Fluoxetine

Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...

), or any medication which affects the electrical impulses to the heart (e.g. astemizole

Astemizole

Astemizole was a second generation antihistamine drug which has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977...

, halofantrine

Halofantrine

Halofantrine is a drug used to treat malaria. Halofantrine's structure contains a substituted phenanthrene, and is related to the antimalarial drugs quinine and lumefantrine. Marketed as Halfan, halofantrine is never used to prevent malaria and its mode of action is unknown...

 or terfenadine

Terfenadine

Terfenadine is an antihistamine formerly used for the treatment of allergic conditions. It was brought to market by Hoechst Marion Roussel and marketed under various brand names including Seldane in the United States, Triludan in the United Kingdom, and Teldane in Australia...

).

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:
Zirkle, C. L.; 1971, .

Dosulepin is also the dibenzothiepine analogue of doxepin

Doxepin

Doxepin is a psychotropic agent with tricyclic antidepressant and anxiolytic properties, known under many brand-names such as Aponal, the original preparation by Boehringer-Mannheim, now part of the Roche group; Adapine, Doxal , Deptran, Sinquan and Sinequan...

, from which it differs by the replacement of the oxygen position with that of sulfur.