How does it work?
Anafranil capsules contain the active ingredient clomipramine, which is a type of medicine called a tricyclic antidepressant (TCA). This type of medicine acts on nerve cells in the brain. (NB. Clomipramine 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.
Clomipramine 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, clomipramine helps relieve depression.
Clomipramine also blocks receptors in other areas of the body, and this can cause side effects such as drowsiness. This means clomipramine may be particularly useful in treating depression in people who are also anxious and agitated.
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.
Clomipramine may also be used in the treatment of obsessive disorders such as obsessive-compulsive disorder and phobia disorders. It is not fully understood how clomipramine works in these conditions but it is thought to be related to the increased effect of serotonin and noradrenaline in the brain. The first few days of clomipramine therapy for these disorders may involve an increase in anxiety and panic, however, this generally gets better within the first two weeks of treatment.
In addition, clomipramine may be used to treat cataplexy (sudden muscle weakness) associated with narcolepsy. Clomipramine is thought to be of use in this condition by increasing the stimulating effect of the chemical noradrenaline in the brain.
What is it used for?
- Depressive illness.
- Phobic or obsessional disorders.
- Sudden muscle weakness (cataplexy), associated with a disorder in which there are repeated attacks of extreme sleepiness (narcolepsy).
- Depression and other psychiatric illnesses are associated with an increased risk of suicidal thoughts, self-harm, and suicide. You should be aware that this medicine may not start to make you feel better for at least two to four weeks. However, it is important that you keep taking it in order for it to work properly and for you to feel better. If you feel your depression has got worse, or if you have any distressing thoughts or feelings, particularly about suicide or harming yourself in these first few weeks, or indeed at any point during treatment or after stopping treatment, then it is very important to talk to your doctor.
- This medicine may cause drowsiness and could reduce your ability to drive or operate machinery safely. Do not drive or operate machinery until you know how this medicine affects you and you are sure it won't affect your performance.
- It is recommended that you avoid drinking alcohol while taking this medicine because it may enhance drowsiness.
- This medicine can occasionally cause your blood pressure to drop when you move from a lying down or sitting position to sitting or standing, especially when you first start taking the medicine. This may make you feel dizzy or unsteady. To avoid this try getting up slowly. If you do feel dizzy, sit or lie down until the symptoms pass.
- Antidepressants may cause the amount of sodium in the blood to drop - a condition called hyponatraemia. This can cause symptoms such as drowsiness, confusion, muscle twitching or convulsions. Elderly people may be particularly susceptible to this effect. You should consult your doctor if you develop any of these symptoms while taking this medicine so that your blood sodium level can be checked if necessary.
- People who wear contact lenses should be aware that this medicine can cause dry eyes, and that wearing contact lenses during treatment may therefore irritate the surface of the eye. If you experience this, consult your doctor.
- This medicine can cause a dry mouth, which may increase the risk of tooth decay with long-term use of the medicine. It is therefore important to visit your dentist regularly for check-ups.
- You should not suddenly stop taking this medicine, as this can cause withdrawal symptoms such as nausea, vomiting, loss of appetite, headache, giddiness, chills, insomnia, restlessness or anxiety. Withdrawal symptoms are temporary and are not due to addiction or dependence on the medicine. They can usually be avoided by stopping the medicine gradually, usually over a period of weeks or months, depending on your individual situation. Follow the instructions given by your doctor when it is time to stop treatment with this medicine.
- During long-term treatment with this medicine your doctor may want to monitor your heart and liver function and take blood tests to monitor the levels of blood cells in your blood. You should let your doctor know if you experience symptoms such as a fever or sore throat while you are taking this medicine.
- This medicine is not recommended for treating children under 18 years of age, because it may increase the risk of anger, aggression or suicidal thoughts in this age group. However, specialists may sometimes still prescribe this medicine for some children and young people if they feel it is necessary. If your child has been prescribed this medicine you should encourage them to tell you if they have any distressing thoughts or feelings after starting it. It is very important that you let their doctor know immediately if you notice any worsening in your child's mood or behaviour.
Use with caution in
- Elderly people.
- Young adults.
- People with a history of suicidal behaviour or thoughts.
- Bipolar affective disorder (manic depression).
- Psychotic illness, eg schizophrenia.
- People receiving electroconvulsive therapy (ECT).
- Liver disease.
- Heart disease.
- Low blood pressure (hypotension).
- History of epilepsy.
- People at risk of seizures (fits), eg due to alcohol/drug withdrawal, brain damage, other medicines.
- History of increased pressure within the eye, eg glaucoma.
- History of difficulty passing urine (urinary retention).
- Enlarged prostate gland (prostatic hypertrophy).
- Long-term ongoing constipation.
- Overactive thyroid gland (hyperthyroidism).
- People taking thyroid medication for an underactive thyroid gland (hypothyroidism).
- Tumour of the adrenal gland (phaeochromocytoma).
- Hereditary blood disorders called porphyrias.
Not to be used in
- Allergy to other tricyclic antidepressants.
- 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).
- Low level of potassium in the blood (hypokalaemia).
- Severe liver disease.
- Closed angle glaucoma.
- Difficulty in passing urine (urinary retention).
- People who have taken a monoamine oxidase inhibitor antidepressant (MAOI) in the last three weeks.
- This medicine is not recommended for treating children under 18 years of age (see warning above).
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 during pregnancy has not been established. It should not be used during pregnancy unless considered essential by your doctor. This is particularly important in the first and third trimesters. Seek medical advice from your doctor.
- This medicine passes into breast milk. The manufacturer recommends that mothers should either avoid using this medicine while breastfeeding, or if they need to keep taking the medicine, avoid breastfeeding. It is important to seek medical advice from your doctor.
- This medication may cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink.
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.
- Gut disturbances such as constipation, nausea, vomiting.
- Blurred vision.
- Difficulty in passing urine (urinary retention).
- Changes in appetite.
- Sleep disturbances.
- Hot flushes.
- Involuntary muscle movements such as tremors or twitching.
- Weight gain.
- Sexual problems.
- Taste disturbance.
- Sensation of ringing or other noise in the ears (tinnitus).
- Drop in blood pressure when going from lying or sitting to sitting or standing, causing dizziness and lightheadedness (postural hypotension).
- Abnormal heart beats.
- 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.
Clomipramine should not be taken in combination with a monoamine oxidase inhibitor antidepressant (MAOI), eg phenelzine, tranylcypromine, isocarboxazid, or moclobemide. Treatment with clomipramine should not be started until at least three weeks after stopping an MAOI. Conversely, an MAOI should not be started until three weeks after stopping clomipramine. Moclobemide should not be started until at least a week after stopping clomipramine.
SSRI antidepressants such as paroxetine, fluvoxamine and fluoxetine increase the blood level of clomipramine. This may increase the risk of side effects. Clomipramine should not be taken within two to three weeks of taking fluoxetine.
If clomipramine is taken with other medicines that enhance serotonin 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:
- SSRI antidepressants, eg fluoxetine, paroxetine
- SNRI antidepressants, eg duloxetine, venlafaxine
- other tricyclic antidepressants.
There may be an increased risk of drowsiness if clomipramine is taken in combination with other medicines that can cause drowsiness, such as the following:
- 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 clomipramine 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 clomipramine)
- 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 clomipramine is taken in combination with the following medicines; these medicines should be avoided in people taking clomipramine:
- 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
Clomipramine 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.
Clomipramine 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 clomipramine. These medicines should be avoided in people taking clomipramine.
The following medicines may increase the blood level of clomipramine and could increase the risk of its side effects:
- calcium channel blockers such as diltiazem or verapamil
- oestrogen-containing contraceptives (these may also decrease the antidepressant effect of clomipramine)
The level of clomipramine in the blood may be decreased by the following medicines, and these could make it less effective:
- barbiturates such as phenobarbital
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.
Other medicines containing the same active ingredient
Clomipramine capsules are also available without a brand name, ie as the generic medicine.