Anafranil

Anafranil is a trade name for a drug whose active ingredient is clomipramine. Clomipramine belongs to the class of tricyclic antidepressants (TCAs) and is used to treat a variety of mental and neurological conditions.

Clomipramine inhibits the reuptake of serotonin and norepinephrine in neurons of the central nervous system, which increases the concentration of these neurotransmitters in the synaptic cleft and enhances their action. It also has anticholinergic, antihistamine and sedative effects.

Indications Anafranil

1. Depression: Anafranil can be used to treat various forms of depression, including major depressive disorder (MDD).
2. Obsessive-compulsive disorder (OCD): This drug is widely used to treat OCD, a serious mental health condition characterized by intrusive thoughts (obsessions) and compulsive actions (compulsions).
3. Panic attacks: Anafranil can be used to treat panic disorder with or without agoraphobia.
4. Anxiety Disorders: It can also be used to treat various anxiety disorders.
5. Natural enuresis (bedwetting): In children and adolescents, Anafranil can be used to treat bedwetting.

Release form

Tablets: This is the most common form of release and is taken orally (by mouth). Tablets may be available in different dosages.

Pharmacodynamics

1. Blocking the reuptake of neurotransmitters: Clomipramine prevents the reuptake of the neurotransmitters serotonin and norepinephrine into the synaptic clefts. This results in increased levels of these neurotransmitters in the brain, which can improve mood and reduce symptoms of depression.
2. Adrenergic receptor blocking: Clomipramine also has adrenergic receptor antagonist activity, which may provide additional antidepressant effects.
3. Serotonin receptor blocking: Some studies suggest that clomipramine may also act on serotonin receptors, although the mechanism of this action is not fully understood.

Pharmacokinetics

1. Absorption: After oral administration, clomipramine is rapidly and completely absorbed from the gastrointestinal tract. However, absorption may be altered by individual factors such as the presence of food in the stomach.
2. Metabolism: Clomipramine is metabolized in the liver by cytochrome P450, mainly by demethylation and hydroxylation. The resulting metabolites have lower activity than clomipramine itself.
3. Bioavailability: The oral bioavailability of clomipramine is approximately 50-60% due to extensive first-pass metabolism in the liver.
4. Distribution: Clomipramine is highly bound to plasma proteins (approximately 97-98%). It has a large volume of distribution, meaning that it can be distributed widely throughout the body.
5. Excretion: Clomipramine and its metabolites are excreted primarily via the kidneys as conjugates and unmetabolized forms. Its half-life is approximately 19-37 hours.
6. Metabolites: The major metabolites of clomipramine are desmethylclomipramine (norclomipramine) and hydroxyclomipramine. They also have antidepressant activity, although to a lesser extent than clomipramine itself.

Dosing and administration

1. Initial Dosage: The usual starting dose for adults is 25 mg 1-3 times daily. This dose may be gradually increased under the supervision of a physician.
2. Maintenance dose: The usual maintenance dose for adults is 50-100 mg per day, divided into several doses.
3. Maximum Dose: The maximum recommended daily dose for adults is usually no more than 250 mg, but in some cases it may reach 300 mg per day.
4. Dosage for children: The dosage for children is usually lower and should be prescribed individually depending on the age and weight of the child.
5. Duration of the course: The duration of the course of treatment is determined by the doctor and can be long, including several months or even years, depending on how well the patient responds to the treatment.

The drug should be taken orally, preferably with food or immediately after a meal to reduce possible irritation of the gastric mucosa. To avoid missing doses, the drug should be taken at the same time every day.

Use Anafranil during pregnancy

1. Neonatal effects:

   • Treatment of pregnant women with clomipramine may cause neonatal problems. Several cases have been described in which neonates whose mothers took clomipramine during pregnancy had symptoms such as respiratory distress, irritability, and tremors (Ostergaard & Pedersen, 1982).

2. Toxic effects:

   • Studies have shown that clomipramine may cause toxic effects in neonates, including decreased muscle tone, difficulty breathing, and drowsiness. These effects may be related to the plasma drug concentrations in neonates (Schimmell et al., 1991).

3. Risks of congenital anomalies:

   • There is an increased risk of congenital malformations with clomipramine use during the period of organogenesis (first trimester of pregnancy). This risk is similar to that associated with other tricyclic antidepressants and serotonin reuptake inhibitors (SSRIs) (Tango et al., 2006).

Contraindications

1. Individual intolerance: Patients with a known allergy to clomipramine or other components of the drug should not use it.
2. Use of monoamine oxidase inhibitors (MAOIs): Anafranil is contraindicated in combination with monoamine oxidase inhibitors and for 14 days after stopping their use, as it may lead to serious side effects such as serotonin syndrome.
3. Acute myocardial infarction: The drug should be used with caution or avoided altogether in the acute stage of myocardial infarction.
4. Acute alcohol intoxication: Use may be undesirable in acute alcohol intoxication due to the possibility of increased sedative effect.
5. High blood pressure: Clomipramine may increase blood pressure and should be used with caution in patients with hypertension.
6. Closed-angle glaucoma: The drug is contraindicated in closed-angle glaucoma due to the risk of increased intraocular pressure.
7. Other conditions: Avoid use in patients with active epilepsy or in cases of acute agitation or aggression.

Side effects Anafranil

1. Drowsiness and fatigue: These are some of the most common side effects of tricyclic antidepressants, including Anafranil.
2. Dry mouth: Increased secretion of antimucous fluid can cause dry mouth.
3. Constipation or problems urinating: Clomipramine may decrease bowel movements and increase bladder tone.
4. Increase or decrease in blood pressure: Some patients may develop hypertension, while others may develop hypotension.
5. Loss of appetite or weight gain: Anafranil may cause both loss of appetite and weight gain in different patients.
6. Decreased libido and sexual dysfunction: This can include both decreased sex drive and problems with erection or orgasm.
7. Tremor, dizziness and headache: These symptoms may occur early in treatment and usually decrease as the dose is increased.
8. Dry Eye: Some patients may experience increased dry eye.
9. Psychomotor retardation: This condition is characterized by slow thinking and movements.
10. Psychiatric reactions: Include anxiety, restlessness, insomnia, agitation, aggression, or the possibility of worsening depressive symptoms.

Overdose

1. Cardiac arrhythmias, including tachycardia (fast heartbeat) or arrhythmias such as atrial fibrillation or ventricular fibrillation.
2. Significant reduction in blood pressure.
3. Pulmonary edema.
4. Dizziness and drowsiness.
5. Loss of consciousness.
6. Cramps.
7. Increased intraocular pressure.
8. Acute mental activity, including aggression or agitation.
9. Difficulty breathing.

Interactions with other drugs

1. Monoamine oxidase inhibitors (MAOIs): Concomitant use of clomipramine with MAOIs may result in serious side effects such as hypertension (high blood pressure) and serotonin syndrome. Before starting treatment with clomipramine, you must stop taking the MAOI and wait for the period of time specified in the instructions for the drug before starting treatment with clomipramine.
2. Alcohol and sleeping pills: Clomipramine increases the depressant effects of alcohol and other drugs that depress the central nervous system (such as sleeping pills), which can lead to drowsiness and increased side effects.
3. Anticholinergic drugs: Clomipramine enhances the anticholinergic effects of other drugs such as antihistamines, antidepressants, and antidepressants, which may lead to increased dry mouth, constipation, urinary retention, and other adverse effects.
4. Sympathomimetics: Clomipramine may enhance the effects of sympathomimetics such as epinephrine and norepinephrine, which may lead to an increase in blood pressure.
5. Antiarrhythmic drugs: Clomipramine may alter electrocardiographic parameters, which may lead to serious arrhythmias when taken concomitantly with antiarrhythmic drugs.