Paroxetine

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) and is approved in Germany for the following indications: depressive disorders, generalized anxiety disorder, panic disorder with or without agoraphobia, social phobia, post-traumatic stress disorder, and obsessive-compulsive disorder. In dermatology, an indication has been reported for the treatment of refractory rosacea erythema (Wang B et al. (2023) .

After oral administration, paroxetine undergoes first-pass metabolism. After administration of higher single doses or after multiple doses, there may be a disproportionate increase in the absolute bioavailability of the active substance and consequently non-linear kinetics. However, this is usually only slight. Approximately 95% of the paroxetine present in plasma is protein-bound (in the therapeutic concentration range). Elimination half-life is variable, but is usually about one day. Excretion is renal and via bile in the feces.

Paroxetine belongs to the group of antidepressants and psychoanaleptics. The active ingredient is used in the treatment of depression, obsessive-compulsive disorder, panic disorder with or without agoraphobia, social anxiety disorder/social phobia, and generalized anxiety disorder.

Paroxetine should be taken once daily, together with breakfast in the morning. The film-coated tablet should be swallowed whole. The dosage of paroxetine depends on the clinical picture.

Paroxetine should be taken once daily, along with breakfast in the morning. The film-coated tablet should be swallowed whole. The dosage of paroxetine depends on the clinical picture.

The recommended active dose for depressive disorders is usually 20 mg per day. The dosage should be reviewed 3-4 weeks after starting therapy and adjusted if necessary. The dose can be increased in 10 mg increments up to a maximum of 50 mg paroxetine per day.

For rosacea, 25mg/day per os has been recommended (Wang B et al. 2023)

Therapy with paroxetine can lead to a wide range of side effects. The following is a list according to the frequency of possible side effects.

Very common

• Difficulty concentrating
• Nausea
• Sexual dysfunction.
• Frequently
• Increase in cholesterol levels
• Decreased appetite
• Sleepiness
• Insomnia
• agitation
• unusual dreams (including nightmares)
• dizziness
• tremor
• headache
• blurred vision
• Yawning
• constipation, diarrhea
• Vomiting
• Dry mouth
• Sweating
• Weakness
• Weight gain.

Occasionally

• abnormal bleeding, especially of the skin and mucous membranes (ecchymosis)
• altered blood sugar levels in diabetics
• States of confusion
• Hallucinations
• extrapyramidal disorders
• mydriasis
• Sinus tachycardia
• Occasional increase or decrease in blood pressure, orthostatic hypotension
• Skin rash
• Itching
• Urinary retention
• Urinary incontinence.

Rarely

• Hyponatremia (especially in elderly patients, sometimes in combination with syndrome of inadequate ADH secretion).
• Manic reactions
• Anxiety
• Depersonalization/alienation experience
• Panic attacks
• Akathisia
• Seizures
• Restless Legs Syndrome (RLS)
• Bradycardia
• Elevation of liver enzyme levels
• hyperprolactinemia/galactorrhea
• Arthralgia, myalgia.

Very rarely

• Thrombocytopenia
• Severe, possibly lethal allergic reactions (including anaphylactoid reactions and Quincke's edema).
• Syndrome of inadequate ADH secretion
• Serotonin syndrome (especially with concomitant use of other serotonergic and/or neuroleptic agents)
• Acute glaucoma
• Gastrointestinal bleeding
• Liver disease (for example, hepatitis, liver failure)
• Serious adverse reactions (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis, phosensitivity syndrome)
• Priapism
• Peripheral edema.
• Side effects of unknown frequency
• Suicidal ideation (especially in adolescents with depressive disorders, young adults 18 to 24 years of age, and adults with depressive disorders)
• Aggression
• Bruxism
• Tinnitus.

Paroxetine may have various interactions with other substances.

Serotonergic substances: concomitant use of paroxetine and serotonergic substances (e.g. triptans, tramadol, linezolid, methylene blue, lithium, etc.) may lead to the occurrence of 5-HAT-associated effects (serotonin syndrome). Therefore, the concomitant use of paroxetine and MAO inhibitors is contraindicated.

Pimozide: Concomitant use of pimozide and paroxetine is contraindicated due to the risk of QT time prolongation.

Fosamprenavir/ritonavir: Decreased paroxetine levels have been observed with concomitant use of fosamprenavir/ritonavir and paroxetine.

Pravastatin: If pravastatin and paroxetine are taken concomitantly, an increase in blood glucose levels may occur. Adjustment of antidiabetic drug dosage must be made in diabetic patients.

Procyclidine: Paroxetine results in an increase in procyclidine levels when the two agents are taken concomitantly. If anticholinergic effects occur, the procyclidine dose must be reduced.

Inhibition of CYP2D6 enzyme by paroxetine: Inhibition of CYP2D6 enzyme by paroxetine may result in an increase in plasma levels of concomitantly used drugs. This may occur, for example, with tricyclic antidepressants (e.g., clomipramine, nortriptyline), phenothiazine neuroleptics (e.g., perphenazine), risperidone, atomoxetine, certain type Ic antiarrhythmics (e.g., flecainide), and metoprolol.

Furthermore, paroxetine-induced CYP2D6 inhibition may result in decreased plasma concentrations of an important active metabolite of tamoxifen, endoxifen.

Alcohol: Alcohol should be avoided during treatment with paroxetine.

Oral Anticoagulants: Concomitant treatment with paroxetine and oral anticoagulants may result in increased anticoagulation and bleeding tendency. Paroxetine should therefore be used with great caution in patients on oral anticoagulation.

Non-steroidal anti-inflammatory drugs, acetylsalicylic acid and other antiplatelet agents: An increased bleeding tendency may occur during concomitant therapy with paroxetine and non-steroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid and other antiplatelet agents. Caution should also be exercised in the concomitant treatment of paroxetine and drugs that affect platelet function or increase the risk of bleeding.

Fluoxetine and paroxetine inhibit the cytochrome P450 isoenzyme CYP2D6

Fluvoxamine inhibits CYP1A2 as well as CYP2C19

Citalopram, escitalopram and sertraline have a low interaction potential

1. Oransky (2003) FDA questions antidepressant safety for children. Lancet 362; 1558
2. Paroxetine (2003) Unfavourable risk benefit ratio in children and adolescents. WHO Pharmaceuticals Newsletter, No. 4, p. 2.
3. Paroxetine ((2003)- Not for under 18-year-olds. "Safer prescribing," 138th Ep. Rheinisches Ärzteblatt, issue 10
4. Waechter, F.: Paroxetine must not be given to patients under 18. BMJ, Vol. 326, p. 1282 (2003).
5. Wang B et al. (2023) Paroxetine is an effective treatment for refractory erythema of rosacea: Primary results from the Prospective Rosacea Refractory Erythema Randomized Clinical Trial. J Am Acad Dermatol 88:1300-1307.