Paroxetine

Paroxetine is an active ingredient for the treatment of depression, post-traumatic stress disorder and anxiety, panic and obsessive-compulsive disorders. It belongs to the group of serotonin reuptake inhibitors (SSRIs). Paroxetine is usually available as a white crystalline (crystal-forming) powder. It is very potent and acts specifically (selectively) on the serotonin transporter SERT in the synaptic cleft. However, due to its very potent effect, withdrawal symptoms can also be more severe if the drug is suddenly discontinued.

Paroxetine works by inhibiting the serotonin transporter (SERT). This transporter is responsible for transporting the monoamine serotonin out of the synaptic cleft. Its inhibition leads to an increased concentration of serotonin in the synaptic cleft.

It is assumed that a lack of monoamines such as noradrenaline or serotonin prevails in the synaptic cleft in cases of depression. Paroxetine is used to counteract this deficiency by inhibiting SERT, which pumps monoamines out of the synaptic cleft. As paroxetine is a CYP2D6 inhibitor, there are increased side effects and interactions with other medications.

Paroxetine is metabolized via the liver, via the enzymes CYP2D6 and CYP3A4. The bioavailability of paroxetine, i.e. the percentage of the active substance that is available in the blood, is 30-60%. The half-life, i.e. the time the body needs to excrete half of the active substance, is approx. 21 hours.

The maximum plasma concentration (Cmax), i.e. the maximum concentration of the active substance in the blood plasma (liquid cell-free part of the blood), is reached after 2-8 hours. Paroxetine must be taken for some time before it develops its full effect. This is also known as the steady-state concentration. This is reached after 7-14 days. Paroxetine is excreted in the urine through the kidneys or feces.

Always take paroxetine exactly as described in the package leaflet or as advised by your doctor.

The usual recommended starting dose is 7.5 mg - 25 mg daily, depending on the clinical picture or tablet type (normal or retard).

The recommended maintenance dose is 10 mg - 50 mg daily, depending on the clinical picture and type of tablet.

The maximum dose is 25 mg - 75 mg daily, depending on the clinical picture and type of tablet.

It is important to note that antidepressants (including paroxetine) usually only develop their full effect after a few weeks, which can lead to a delayed onset of action.

It is also important to note that antidepressants (including paroxetine) should never be discontinued suddenly, but must always be phased out. Tapering means that the dose is gradually and slowly reduced until you can stop taking it altogether. Your doctor will tell you how much the dose should be reduced.

The following side effects may occur:

Very common:

• Nausea
• Disorders in sexual desire or sexual function

Frequent:

• Increase in cholesterol levels
• Loss of appetite
• sleep disturbances
• Abnormal dreams
• dizziness
• trembling
• headaches
• concentration problems
• excitement
• Feeling weak
• blurred vision
• yawning
• dry mouth
• diarrhea
• constipation
• vomiting
• weight gain
• sweating

Occasionally:

• Bleeding or bruising
• Difficulty urinating
• drop in blood pressure
• Increased heart rate
• restricted mobility
• dilated pupils
• skin rashes
• itching
• confusion
• hallucinations
• Changes in blood sugar levels

Rarely:

• Seizures
• Restlessness (akathisia)
• tiredness
• Abnormal milk secretion from the mammary gland in men and women
• slow heartbeat
• change in blood liver values
• panic attacks
• mania
• Feeling of strangeness towards oneself
• feelings of anxiety
• compulsions
• Joint and/or muscle pain
• Increase in the prolactin level in the blood
• Menstrual disorders

Very rare:

• Allergic reactions
• serotonin syndrome
• neuroleptic syndrome
• glaucoma
• Blistering of the skin
• liver diseases
• Syndrome of inadequate ADH secretion (SIADH)
• Fluid retention
• Sensitivity to sunlight
• painful permanent erection of the penis
• Decreased blood platelet count

Frequency not known:

• suicidal thoughts
• thoughts of self-harm
• aggression problems
• teeth grinding
• Noises in the ears (tinnitus)
• colitis
• Heavy vaginal bleeding shortly after birth

Interactions may occur if the following medicines are taken at the same time:

• Monoamine oxidase inhibitors (MAOIs)
• thioridazine
• pimozide
• Acetylsalicylic acid, ibuprofen or other non-steroidal anti-inflammatory drugs (NSAIDs)
• tramadol
• pethidine
• triptans
• Other antidepressants (SSRIs and tricyclic antidepressants)
• tryptophan
• mivacurium
• suxamethonium
• lithium
• risperidone
• perphenanzine
• clozapine
• fentanyl
• Fosamprenavir and ritonavir
• St. John's wort
• Phenobarbital
• phenytoin
• Sodium valproate
• carbamazepine
• atomoxetine
• procyclidine
• warfarin or other medicines to thin the blood
• Propafenone, flecainide or other medicines for the treatment of cardiac arrhythmias
• metoprolol
• pravastatin
• rifampicin
• linezolid
• Tamoxifen
• Alcohol

Paroxetine must NOT be taken in the following cases:

• when taking monoamine oxidase inhibitors (MAO inhibitors including moclobemide and methylthionium chloride), even if the last dose was taken less than 2 weeks ago
• if taking thioridazine or pimozide
• allergy to paroxetine

Paroxetine should NOT be used under the age of 18.

Pregnancy

During pregnancy, paroxetine should only be taken if switching to other antidepressants is too complicated and proves to be disadvantageous for the patient.

A risk of malformation cannot be ruled out in the first trimester of pregnancy . In addition, the risk of cardiac malformations after paroxetine is increased in the 1st trimester of pregnancy.

In the 2nd and 3rd trimester of pregnancy, serotonergic toxicity may occur in the baby after birth. Symptoms of this include tremors, drinking disorders, hyperexcitability, shortness of breath, hypoglycemia and abnormal sleeping patterns. These symptoms usually begin in the first few days of life and can last up to a month.

Sertraline or citalopram can be used as an alternative during pregnancy.

If the drug is nevertheless taken during pregnancy, a neonatal clinic should be used.

Breastfeeding

Paroxetine can be taken while breastfeeding , as it does not pass into breast milk, or only in quantities below the detection limit. Paroxetine is the drug of choice during breastfeeding.