Paroxetine is an antidepressant drug belonging to the selective serotonin reuptake inhibitor (SSRI) class. Within its structure, paroxetine has two chiral centers that give rise to four different stereoisomers. Only the enantiomer (3S, 4R) - (-) is marketed.
Paroxetine - Chemical Structure
Paroxetine has a high affinity towards the serotonin reuptake transporter (SERT) and is much more powerful and selective than fluoxetine (another SSRI antidepressant).
Like all drugs belonging to the SSRI class, paroxetine is also preferred to tricyclic antidepressants (TCAs) thanks to better tolerability and reduced side effects compared to the latter.
Indications
For what it uses
The use of paroxetine is indicated for the treatment of the following diseases:
- Episodes of major depression;
- Obsessive-compulsive disorder;
- Disorder from panic attacks, with or without agoraphobia;
- Social anxiety disorder or social phobia;
- Generalized anxiety disorder;
- Post-traumatic stress disorder.
Warnings
If you suffer from depression there may be an increased risk of witty thoughts, self-harm and suicide attempt. Since paroxetine requires a period of 1-4 weeks before manifesting its therapeutic action, it is necessary for patients to be carefully monitored until there is a significant improvement in the symptoms mentioned above.
Paroxetine should not be used in patients under 18 years of age. However, if the doctor considers it absolutely necessary, he could also prescribe paroxetine to this category of patients. It is important to know that the use of paroxetine by these patients may increase the risk of developing suicidal thoughts, suicide attempts and hostility.
When patients enter a manic phase, paroxetine treatment should be discontinued.
Caution should be used in the administration of paroxetine in patients suffering from pre-existing liver and / or renal diseases, especially if they are severe.
Since paroxetine can alter blood glucose levels, dose adjustments of insulin and / or antidiabetic drugs administered may be necessary in diabetic patients.
Because paroxetine can cause seizures, care must be taken when administering the drug to patients with epilepsy.
A great deal of caution should be used when administering paroxetine in patients treated with electroconvulsive therapy (TEC).
Paroxetine may cause increased internal eye pressure, so care must be taken when administering it to patients with glaucoma.
Attention should be paid to the administration of paroxetine in patients with previous heart conditions.
Paroxetine may increase the risk of bleeding, so if abnormal bleeding occurs, you should immediately tell your doctor.
Before stopping treatment with paroxetine it is necessary to consult a doctor, as the abrupt withdrawal of therapy could cause withdrawal symptoms.
Interactions
Concomitant administration of paroxetine and the following drugs may lead to the onset of serotonergic syndrome, therefore their association should be avoided:
- IMAO (monoamine oxidase inhibitors), such as moclobemide ;
- Tryptophan ;
- Triptans (drugs used in the treatment of migraine), such as - for example - sumatriptan and almotriptan ;
- Tramadol, an opioid analgesic;
- Linezolid, an antibiotic;
- Methylene blue, a pre-operative highlighter agent;
- Other SSRIs, such as fluoxetine, sertraline and fluvoxamine ;
- Lithium, a drug used in the treatment of bipolar disorders;
- Fentanyl, an opiate painkiller;
- Hypericum based preparations (or St. John's wort), a plant with antidepressant properties.
Paroxetine can cause an increase in blood levels of pimozide (a drug used to treat psychosis), therefore, the simultaneous intake of these two drugs should be avoided.
Since paroxetine is metabolised by liver enzymes, caution should be used in the concomitant administration of drugs capable of inhibiting these enzymes.
Paroxetine can interact with some drugs used to treat AIDS, such as - for example - ritonavir .
Paroxetine can enhance the effectiveness - and at the same time the side effects - of the following drugs:
- Procyclidine (a drug used to relieve symptoms of Parkinson's disease);
- Tricyclic antidepressants, such as imipramine and clomipramine ;
- Antipsychotic drugs, such as perphenazine, thioridazine and risperidone ;
- Drugs for the treatment of children with ADHD (attention deficit / hyperactivity disorder), such as atomoxetine ;
- Antiarrhythmics, such as flecainide ;
- Metoprolol, a drug used to treat angina pectoris and hypertension;
- Phenotiazine, a group of molecules with antipsychotic and antihistamine action;
- Anticoagulant drugs, such as - for example - acenocoumarol .
Paroxetine can interact with tamoxifen, an anticancer medicine used to treat breast cancer.
Care should be taken when administering paroxetine in patients taking drugs that can increase the risk of bleeding, including:
- Phenothiazines, such as - for example - chlorpromazine ;
- Clozapine, a drug used to treat schizophrenia;
- Tricyclic antidepressants ;
- Acetylsalicylic acid ;
- NSAIDs (non-steroidal anti-inflammatory drugs), such as - for example - ibuprofen or celecoxib .
Concomitant intake of paroxetine and alcohol should be avoided.
Paroxetine could cause side effects that affect the ability to drive or use machines, so caution is required.
In any case, it is advisable to inform your doctor if you are taking - or have recently been - other medicines of any kind.
Side effects
Paroxetine may induce various side effects, although not all of them occur. In fact, each patient has his own sensitivity to the drug and it is not said that the side effects occur all with the same intensity in each individual.
The following are the main side effects that may occur following treatment with paroxetine.
Blood and lymphatic system disorders
Treatment with paroxetine can cause disorders of the blood cell production system (hemolymphopoietic system). These disorders can give rise to thrombocytopenia, ie a reduced concentration of platelets in the bloodstream. This reduction increases the risk of bruising, abnormal bleeding and / or bleeding.
Allergic reactions
Paroxetine can trigger allergic reactions in sensitive individuals. These reactions can occur in the form of hives or itching. Or the swelling of the throat, tongue or skin may occur with consequent difficulty in breathing and / or itching.
Endocrine disorders
Paroxetine therapy can cause the syndrome of inappropriate antidiuretic hormone secretion (SIADH) which - in turn - could lead to the appearance of water retention and hyponatremia (lowering of blood sodium levels).
Metabolism and nutrition disorders
Paroxetine can cause an increase in blood cholesterol levels and a reduction in appetite. The drug can also promote hyponatremia, especially in older patients.
Psychiatric disorders
Treatment with paroxetine can cause various psychiatric disorders, including:
- Drowsiness;
- agitation;
- Insomnia;
- Abnormal dreams and nightmares;
- Confusion;
- Hallucinations;
- Manic periods;
- Anxiety;
- Panic attacks;
- depersonalization;
- Restlessness;
- Akathisia, that is the impossibility to sit or stand still;
- Self-injuring and / or suicidal thoughts or behavior.
Nervous system disorders
Among the nervous system disorders that can be induced by paroxetine therapy, we recall:
- Difficulty concentrating;
- dizziness;
- Tremors;
- Headache;
- Extrapyramidal disorders, ie Parkinson-like symptoms;
- Seizures or seizures;
- Restless legs syndrome.
Serotonin syndrome
This syndrome can occur especially if paroxetine is administered concomitantly with drugs that are also able to increase serotonin transmission. It is also referred to as serotonin poisoning and is caused by an excess of serotonin activity in the central nervous system. Serotonin poisoning can occur in mild, moderate or severe form.
The symptoms that can arise are:
- Tachycardia;
- Chills;
- Increased sweating;
- Headache;
- Mydriasis (dilation of the pupils);
- Tremors;
- Myoclonia (short and involuntary contraction of a muscle or a group of muscles);
- spasms;
- Accurate reflexes.
- Accentuation of intestinal sounds (borborigmas);
- Diarrhea;
- Hypertension;
- Temperature.
The patient may also enter a state of shock with body temperatures exceeding 40 ° C.
Rhabdomyolysis (rupture of skeletal muscle cells and release of substances inside the musculature into the bloodstream), convulsions and renal failure may also occur.
Eye disorders
Paroxetine can cause blurred vision and mydriasis (pupil dilation). Furthermore, the drug can also cause a sudden increase in intraocular pressure (acute glaucoma).
Ear disorders
Treatment with paroxetine can give rise to tinnitus, that is to say an auditory disorder characterized by the perception of noises such as buzzing, hissing, hissing, whistling, tinkling, etc.
Cardiovascular disorders
At cardiac level, paroxetine can cause sinus tachycardia or bradycardia.
On the vascular level, however, the drug can cause transient increases or decreases in blood pressure.
Gastrointestinal disorders
After taking paroxetine, nausea, vomiting, diarrhea or constipation and dry mouth may occur. Gastrointestinal bleeding may also occur.
Hepatobiliary disorders
Treatment with paroxetine may cause an increase in blood levels of liver enzymes. Furthermore, the drug could favor the appearance of hepatitis, sometimes associated with jaundice and / or liver failure.
Skin and skin tissue disorders
Paroxetine can cause increased sweating, skin rash, pruritus and photosensitivity reactions. More severe skin reactions may also occur, such as Stevens-Johnson syndrome (a variant of polymorphic erythema) and toxic epidermal necrolysis.
Renal and urinary disorders
Paroxetine therapy can cause retention and urinary incontinence.
Reproductive system and breast disorders
Treatment with paroxetine can cause sexual dysfunction, such as decreased libido, ejaculation problems, male impotence and inability to reach orgasm. Furthermore, paroxetine can induce hyperprolactinaemia (ie an increase in blood levels of the hormone prolactin) which can lead to abnormal secretion of milk (galactorrhoea) in both women and men.
Finally, the drug can induce priapism, a long and painful erection not accompanied by sexual arousal.
Suspension symptoms
If treatment with paroxetine is stopped abruptly, so-called withdrawal symptoms may occur. These symptoms are:
- dizziness;
- Sensory disorders;
- Sleep disorders;
- Anxiety;
- Headache;
- agitation;
- Sweating;
- Tremor;
- Nausea;
- Confusion;
- Emotional instability;
- Palpitations;
- Visual disturbances;
- Diarrhea;
- Irritability.
These symptoms - usually - are self-limiting, but you should still consult your doctor before stopping paroxetine therapy.
Bone fractures
In patients taking paroxetine - or other medicines of this type - an increased risk of bone fractures has been observed.
Other side effects
Other side effects that may occur following paroxetine intake are:
- Frequent yawns;
- Increased body weight;
- Myalgia and / or arthralgia;
- Fatigue;
- Asthenia;
- Peripheral edema.
Overdose
In the event of an overdose of paroxetine it is necessary to immediately contact a doctor or go to the nearest hospital. The symptoms that can occur after taking an overdose are:
- He retched;
- mydriasis;
- Headache;
- Temperature;
- Variations in arterial pressure;
- Anxiety;
- agitation;
- Tachycardia;
- Tremor.
Action mechanism
As mentioned above, paroxetine is a selective inhibitor of serotonin reuptake.
Serotonin (5-HT) is synthesized in the presynaptic nerve endings and released into the synaptic wall (the space between the presynaptic and postsynaptic nerve endings) following certain stimuli.
Once released from the nerve termination, 5-HT interacts with its receptors, both pre- and postsynaptic. After explicating its action, serotonin binds to the transporter that operates its reuptake (the SERT) and is brought back into the presynaptic termination.
Paroxetine is a powerful SERT inhibitor and - by binding to it in place of serotonin - causes it to remain within the synaptic wall for a prolonged time, thus allowing it to continue interacting with its postsynaptic receptors. The enhancement of the induced serotoninergic transmission allows the improvement of the psychiatric pathologies treated.
Mode of Use - Posology
Paroxetine is available for oral administration as tablets. The drug should preferably be taken in the morning on a full stomach. The tablets should be swallowed whole, without chewing.
The dosage of paroxetine must be established by the doctor on an individual basis, depending on the pathology to be treated and the patient's condition.
In case of impaired hepatic and / or renal function an adjustment of the administered dose may be necessary.
The following are the doses of paroxetine usually used.
Major depressive episodes
The usual starting dose of paroxetine is 20 mg of drug, to be taken once a day. The dose can be gradually increased up to a maximum of 50 mg of active ingredient.
Obsessive-compulsive disorder
The dose of drug initially administered is 20 mg of drug per day which can be increased to 40 mg per day, to be administered in divided doses. Your doctor may increase the dose - in case of an inadequate response - up to a maximum of 60 mg of paroxetine a day.
Disorder from panic attacks, with or without agoraphobia
The usual starting dose of paroxetine is 10 mg a day. Subsequently, the amount of drug is increased up to 40 mg, to be administered in two separate doses.
In the event of an inadequate response from the patient, the doctor may decide to gradually increase the dose up to a maximum of 60 mg of paroxetine per day.
Social anxiety disorder / social phobia, generalized anxiety disorder and post-traumatic stress disorder
The recommended paroxetine dose is 20 mg a day. In the event of an inadequate response, the doctor may decide to gradually increase the dose up to a maximum of 50 mg of active ingredient per day.
Use in the elderly
The doses of paroxetine normally used are the same as those used for adult patients, but the maximum daily dose should not exceed 40 mg a day.
Pregnancy and breastfeeding
Studies have shown the risk of developing heart defects in newborns whose mothers took paroxetine during the first months of pregnancy
Furthermore - when medications such as paroxetine are taken in the last trimester of pregnancy - it could increase the risk of the onset of persistent pulmonary hypertension of the newborn (PPHN) manifested by an increase in respiratory rate and a bluish complexion of the skin. In addition, symptoms may occur in the newborn, such as difficulty in falling asleep or feeding, breathing difficulties, cyanosis, unstable body temperature, vomiting, constant crying, muscle stiffness or weakness, lethargy, tremors, nervousness or seizures. Usually, these symptoms occur within 24 hours of birth.
Paroxetine - although in minimal quantities - is excreted in breast milk.
For the reasons mentioned above, pregnant women or breastfeeding mothers should definitely seek advice from their doctor before taking paroxetine and carefully evaluate the benefit-risk ratio that comes with using it.
Contraindications
The use of paroxetine is contraindicated in the following cases:
- Known hypersensitivity to paroxetine;
- In patients already on IMAO therapy;
- In patients taking pimozide (an antipsychotic);
- In patients taking thioridazine (another antipsychotic drug);
- In children and adolescents under the age of 18.
