Drugs List

Therapeutic Indications

Uses

Depressive illness with anxiety

Contraindications

Children under 18 years
Within 2 weeks of discontinuing MAOIs
Within 2 weeks of discontinuing selegiline
Atrioventricular block
Cardiac arrhythmias
Long QT syndrome
Mania
Porphyria
Recent myocardial infarction
Severe hepatic impairment
Torsade de pointes

Precautions and Warnings

Anaesthesia
Elderly
Electroconvulsive therapy
Family history of long QT syndrome
Suicidal ideation
Bipolar disorder
Breastfeeding
Cardiovascular disorder
Electrolyte imbalance
Epileptic disorder
Hepatic impairment
History of mania
History of torsade de pointes
Narrow angle glaucoma
Phaeochromocytoma
Pregnancy
Prostate disorder
Thyroid dysfunction
Urinary retention

Anaesthetist should be made aware patient is taking this medication
Correct electrolyte disorders before treatment
Patients at risk of suicide should be closely supervised
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Consider monitoring ECG in patients at risk of QT prolongation
Monitor for depressive disorders/suicidal ideation-consider discontinuation
Monitor patients at risk of glaucoma for increases in intraocular pressure
Monitor serum electrolytes
Treatment of depression - monitor initially; may take 2-4 weeks to respond
Advise patient to report any new or worsening depression/suicidal ideation
Advise patients/carers to seek medical advice if suicidal intent develops
Consider hyponatraemia in all patients with drowsiness/confusion/seizures
Increased risk of fractures in patients over 50 years
Potential for withdrawal symptoms
Do not withdraw this drug suddenly
Dosage reduction should be done gradually over about 4 weeks
Reduce dose in elderly
Advise patient not to take St John's wort concurrently
Advise patient that the effects of alcohol may be potentiated

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in children and adolescents, antidepressants may increase the risk of suicidal thoughts and self harm

Patients receiving SSRIs or TCAs, mainly those aged 50 years or older - a review of epidemiological studies shows an increased risk of bone fractures in these patients. The mechanism leading to this increased risk is unclear.

Pregnancy and Lactation

Pregnancy

Use dosulepin with caution in pregnancy.

If the mother is using dosulepin before becoming pregnant, treatment should be continued. Evidence suggests that not treating depression during a pregnancy can cause serious harm to the foetus (Schaefer, 2007).
Serum levels of dosulepin can fluctuate during pregnancy meaning that the effective dose the mother receives maybe ineffective at treating symptoms. Serum levels should be monitored and dose adjusted accordingly. Observation of the mother for psychiatric and complications of pregnancy is recommended.

At the time of writing there is insufficient information on the potential effects on the developing foetus. Withdrawal effects have been seen in neonates and it is recommended that they be observed for symptoms for at least two days after birth. Consideration should be given to dose reduction or an interruption in treatment immediately preceding delivery.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use dosulepin with caution in breastfeeding.

Dosulepin is broken down into three active metabolites which are present in breast milk. At the time of writing the is not enough information to assess the effect/s of these metabolites on a nursing infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abnormal liver function tests
Agranulocytosis
Behavioural disturbances
Blood sugar changes
Blurred vision
Bone marrow depression
Cardiac arrhythmias
Cholestatic jaundice
Confusion
Constipation
Convulsions
Delirium
Difficulty in micturition
Disturbances in accommodation
Drowsiness
Dry mouth
Dysarthria
Dyskinesia
ECG changes
Eosinophilia
Fever
Galactorrhoea
Gynaecomastia
Hepatitis
Hypersensitivity reactions
Hypomania
Hyponatraemia
Inappropriate secretion of antidiuretic hormone
Increased appetite
Increased intra-ocular pressure
Increased risk of fractures
Involuntary movement disorders
Leucopenia
Mania
Nausea
Paraesthesia
Paranoid delusions
Photosensitivity
Postural hypotension
Purpura
Rash
Sedation
Severe hypotension
Sexual dysfunction
Sweating
Syncope
Tachycardia
Taste disturbances
Testicular swelling
Thrombocytopenia
Tinnitus
Tremor
Urticaria
Weight gain

Presentation

Oral formulations of dosulepin hydrochloride

Drugs List

Therapeutic Indications

Uses

Depressive illness with anxiety

Dosage

Adults

Elderly

Contraindications

Children under 18 years
Within 2 weeks of discontinuing MAOIs
Within 2 weeks of discontinuing selegiline
Atrioventricular block
Cardiac arrhythmias
Long QT syndrome
Mania
Porphyria
Recent myocardial infarction
Severe hepatic impairment
Torsade de pointes

Precautions and Warnings

Anaesthesia
Elderly
Electroconvulsive therapy
Family history of long QT syndrome
Suicidal ideation
Bipolar disorder
Breastfeeding
Cardiovascular disorder
Electrolyte imbalance
Epileptic disorder
Hepatic impairment
History of mania
History of torsade de pointes
Narrow angle glaucoma
Phaeochromocytoma
Pregnancy
Prostate disorder
Thyroid dysfunction
Urinary retention

Anaesthetist should be made aware patient is taking this medication
Correct electrolyte disorders before treatment
Patients at risk of suicide should be closely supervised
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Consider monitoring ECG in patients at risk of QT prolongation
Monitor for depressive disorders/suicidal ideation-consider discontinuation
Monitor patients at risk of glaucoma for increases in intraocular pressure
Monitor serum electrolytes
Treatment of depression - monitor initially; may take 2-4 weeks to respond
Advise patient to report any new or worsening depression/suicidal ideation
Advise patients/carers to seek medical advice if suicidal intent develops
Consider hyponatraemia in all patients with drowsiness/confusion/seizures
Increased risk of fractures in patients over 50 years
Potential for withdrawal symptoms
Do not withdraw this drug suddenly
Dosage reduction should be done gradually over about 4 weeks
Reduce dose in elderly
Advise patient not to take St John's wort concurrently
Advise patient that the effects of alcohol may be potentiated

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in children and adolescents, antidepressants may increase the risk of suicidal thoughts and self harm

Patients receiving SSRIs or TCAs, mainly those aged 50 years or older - a review of epidemiological studies shows an increased risk of bone fractures in these patients. The mechanism leading to this increased risk is unclear.

Pregnancy and Lactation

Pregnancy

Use dosulepin with caution in pregnancy.

If the mother is using dosulepin before becoming pregnant, treatment should be continued. Evidence suggests that not treating depression during a pregnancy can cause serious harm to the foetus (Schaefer, 2007).
Serum levels of dosulepin can fluctuate during pregnancy meaning that the effective dose the mother receives maybe ineffective at treating symptoms. Serum levels should be monitored and dose adjusted accordingly. Observation of the mother for psychiatric and complications of pregnancy is recommended.

At the time of writing there is insufficient information on the potential effects on the developing foetus. Withdrawal effects have been seen in neonates and it is recommended that they be observed for symptoms for at least two days after birth. Consideration should be given to dose reduction or an interruption in treatment immediately preceding delivery.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use dosulepin with caution in breastfeeding.

Dosulepin is broken down into three active metabolites which are present in breast milk. At the time of writing the is not enough information to assess the effect/s of these metabolites on a nursing infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abnormal liver function tests
Agranulocytosis
Behavioural disturbances
Blood sugar changes
Blurred vision
Bone marrow depression
Cardiac arrhythmias
Cholestatic jaundice
Confusion
Constipation
Convulsions
Delirium
Difficulty in micturition
Disturbances in accommodation
Drowsiness
Dry mouth
Dysarthria
Dyskinesia
ECG changes
Eosinophilia
Fever
Galactorrhoea
Gynaecomastia
Hepatitis
Hypersensitivity reactions
Hypomania
Hyponatraemia
Inappropriate secretion of antidiuretic hormone
Increased appetite
Increased intra-ocular pressure
Increased risk of fractures
Involuntary movement disorders
Leucopenia
Mania
Nausea
Paraesthesia
Paranoid delusions
Photosensitivity
Postural hypotension
Purpura
Rash
Sedation
Severe hypotension
Sexual dysfunction
Sweating
Syncope
Tachycardia
Taste disturbances
Testicular swelling
Thrombocytopenia
Tinnitus
Tremor
Urticaria
Weight gain

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last full review date: January 2015

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 6 January 2015.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Dosulepin capsules 25mg. Teva UK Ltd. Revised November 2013.
Summary of Product Characteristics: Dosulepin tablets BP 75mg. Teva UK Ltd. Revised November 2013.

Summary of Product Characteristics: Prothiaden capsules 25mg. Teofarma. Revised July 2010.
Summary of Product Characteristics: Prothiaden tablets 75mg. Teofarma. Revised July 2010.

MHRA 4th February 2008
https://www.mhra.gov.uk/NewsCentre/Pressreleases/CON2033960
Last accessed 6 January 2015

MHRA Drug Safety Update May 2010
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON081863
Last accessed: 6 January 2015

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Dosulepin Last revised: 7 September 2013
Last accessed: 6 January 2015