Prothiaden capsules and tablets contain the active ingredient dosulepin, which is a type of medicine called a tricyclic antidepressant (TCA). This type of medicine acts on nerve cells in the brain.

What is it used for?

  • Depressive illness.

How does it work?

  • Prothiaden capsules and tablets contain the active ingredient dosulepin (previously known as dothiepin in the UK), which is a type of medicine called a tricyclic antidepressant (TCA). This type of medicine acts on nerve cells in the brain. (NB. Dosulepin is also available without a brand name, ie as the generic medicine.)
  • In the brain there are numerous different chemical compounds called neurotransmitters. These act as chemical messengers between the nerve cells. Serotonin and noradrenaline are neurotransmitters and they have various functions that we know of.
  • When serotonin and noradrenaline are released from nerve cells in the brain they act to lighten mood. When they are reabsorbed into the nerve cells, they no longer have an effect on mood.
It is thought that when depression occurs, there may be a decreased amount of serotonin and noradrenaline released from nerve cells in the brain.
  • Dosulepin works by preventing serotonin and noradrenaline from being reabsorbed back into the nerve cells in the brain. This helps prolong the mood lightening effect of any released noradrenaline and serotonin. In this way, dosulepin helps relieve depression.
  • Dosulepin can cause side effects such as drowsiness. This means it may be useful in treating depression in people who are also anxious and agitated, or who are suffering from disturbances in sleep.
  • It may take between two to four weeks for the benefits of this medicine to appear, so it is very important that you keep taking it, even if it doesn't seem to make much difference at first. If you feel your depression has got worse, or if you have any distressing thoughts or feelings in these first few weeks, then you should talk to your doctor.
  • Use with caution in

    • Elderly people.
    • Decreased liver function.
    • Heart disease.
    • History of difficulty passing urine (urinary retention).
    • Enlarged prostate gland (prostatic hypertrophy).
    • History of increased pressure within the eye, eg glaucoma.
    • History of epilepsy.
    • People at risk of seizures (fits), eg due to alcohol/drug withdrawal, brain damage, other medicines.
    • Overactive thyroid gland (hyperthyroidism).
    • People taking thyroid medication for an underactive thyroid gland (hypothyroidism).
    • Tumour of the adrenal gland (phaeochromocytoma).
    • Psychotic illness, eg schizophrenia.
    • People receiving electroconvulsive therapy (ECT).
    • Bipolar affective disorder (manic depression).
    • Hereditary blood disorders called porphyrias.

    Not to be used in

    • Children.
    • Severe liver disease.
    • People who have recently had a heart attack.
    • Defect of the heart's electrical message pathways resulting in decreased function of the heart (heart block).
    • Irregular heart beats (arrhythmias).
    • Closed angle glaucoma.
    • Manic phase of manic depression.
    • People who have taken a monoamine oxidase inhibitor antidepressant (MAOI) in the last two weeks.

    This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

    If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

    Pregnancy and breastfeeding

    Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

    • The safety of this medicine for use during pregnancy has not been established. It is not recommended for pregnant women, particularly in the first and third trimesters, unless considered essential by your doctor and the benefits to the mother outweigh the potential risks to the unborn baby. Seek medical advice from your doctor.
    • This medicine passes into breast milk. It should be used with caution in mothers who are breastfeeding, and only if the potential benefits outweigh any risks to the nursing infant. Seek medical advice from your doctor.

    Side effects

    Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

    • Dry mouth.
    • Drowsiness.
    • Blurred vision.
    • Constipation.
    • Nausea.
    • Difficulty in passing urine.
    • Drop in blood pressure when going from lying or sitting to sitting or standing, causing dizziness and lightheadedness (postural hypotension).
    • Sweating.
    • Involuntary muscle movements such as tremors or twitching.
    • Rashes.
    • Confusion or delirium.
    • Headache.
    • Sexual problems.
    • Changes in behaviour.
    • Increased appetite and weight gain.
    • Taste disturbances.
    • Low blood pressure (hypotension).
    • Disturbances in the normal numbers of blood cells in the blood.
    • Abnormal heart beats.
    • Faster than normal heart beat (tachycardia).
    • Convulsions (fits).

    The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.

    For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

    How can this medicine affect other medicines?

    It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to ensure that the combination is safe.

    Dosulepin should not be taken in combination with a monoamine oxidase inhibitor antidepressant (MAOI), eg phenelzine, tranylcypromine, isocarboxazid, or moclobemide. Treatment with dosulepin should not be started until at least two weeks after stopping an MAOI. Conversely, an MAOI should not be started until two weeks after stopping dosulepin. Moclobemide should not be started until at least a week after stopping dosulepin.

    If dosulepin is taken with other medicines that enhance serotonin activity in the brain, there may be an increased risk of side effects such as agitation, tremor, shivering, increased heart rate and diarrhoea, known collectively as the 'serotonin syndrome'. Other medicines that increase serotonin activity include the following:

    • lithium
    • rasagiline
    • selegiline
    • sibutramine
    • SSRI antidepressants, eg fluoxetine, paroxetine
    • SNRI antidepressants, eg duloxetine, venlafaxine
    • other tricyclic antidepressants.

    There may be an increased risk of drowsiness if other medicines that can cause drowsiness, such as the following, are taken in combination with dosulepin:

    • sedating antihistamines, eg chlorphenamine, promethazine
    • benzodiazepines, eg diazepam, temazepam
    • sleeping tablets, eg zopiclone
    • strong opioid painkillers, such as morphine, codeine.

    There may be an increased risk of side effects such as dry mouth, constipation, difficulty passing urine and blurred vision if dosulepin is taken with other medicines that have anticholinergic effects, such as the following:

    • anticholinergics for urinary incontinence, eg tolterodine, oxybutynin
    • anticholinergics for Parkinson's disease, eg procyclidine, trihexyphenidyl
    • antihistamines, eg promethazine, chlorphenamine
    • antispasmodics, eg hyoscine, atropine
    • antipsychotics, eg chlorpromazine, clozapine (some antipsychotics may also increase the blood level of dosulepin)
    • antiarrhythmics, eg disopyramide, propafenone
    • certain other antidepressants
    • muscle relaxants, eg baclofen
    • antisickness medicines, eg meclozine, cyclizine.

    There may be an increased risk of side effects on the heart if dosulepin is taken in combination with the following medicines; these medicines should be avoided in people taking dosulepin:

    • atomoxetine
    • medicines to treat abnormal heart rhythms (antiarrhythmics), eg amiodarone, procainamide, quinidine, disopyramide, sotalol
    • the antihistamines astemizole, terfenadine or mizolastine
    • the antimalarials halofantrine, chloroquine or quinine
    • certain antipsychotics, eg thioridazine, haloperidol, pimozide
    • moxifloxacin
    • pentamidine.

    Dosulepin may alter the anti-blood-clotting effect of anticoagulant medicines such as warfarin. Your blood clotting time (INR) should be carefully monitored if you are taking these two medicines together.

    Dosulepin may oppose the blood pressure lowering effects of clonidine and guanethidine.

    There may be a sudden and marked increase in blood pressure and heart rate if adrenaline, noradrenaline or phenylephrine are given by injection to people taking dosulepin. These medicines should be avoided in people taking dosulepin.

    The following medicines may increase the blood level of dosulepin and could increase the risk of its side effects:

    • calcium channel blockers such as diltiazem or verapamil
    • cimetidine
    • methylphenidate
    • oestrogen-containing contraceptives (these may also decrease the antidepressant effect of dosulepin)
    • ritonavir
    • SSRI antidepressants such as fluvoxamine and fluoxetine.

    The level of dosulepin in the blood may be decreased by the following medicines, and these could make it less effective:

    • barbiturates such as phenobarbital
    • rifampicin.

    If you experience a dry mouth as a side effect of this medicine you may find that medicines that are designed to dissolve and be absorbed from under the tongue, eg sublingual glyceryl trinitrate (GTN) tablets for angina, become less effective. This is because the tablets do not dissolve properly in a dry mouth. To resolve this, drink a mouthful of water before taking sublingual tablets.

    References:

    https://en.wikipedia.org/wiki/Dosulepin

    http://www.netdoctor.co.uk/medicines/depression/a7418/prothiaden-dosulepin/

    https://www.drugs.com/uk/prothiaden-tablets-75mg-leaflet.html

    http://www.anti-depressants.com/drugs/tricyclic/dosulepin/