Paroxetine: Uses, Side Effects, Administration, Mechanism of Action and Interactions

It works by helping to restore the balance of a certain natural substance (serotonin) in the brain.

Uses of Paroxetine

Paroxetine is used to treat depression , panic attacks , obsessive compulsive disorder (OCD), anxiety disorders, and post- traumatic stress disorder.

How does paroxetine work?

Paroxetine hydrochloride is a type of antidepressant medication known as a selective serotonin reuptake inhibitor (SSRI). It works by enhancing the activity of a neurotransmitter called serotonin in the brain.

Neurotransmitters are natural chemicals in the body that act as chemical messengers between nerve cells.

Serotonin is a neurotransmitter known to be involved in the regulation of emotions, mood, and behavior, among other things. In depression and anxiety disorders, there is less serotonin released by nerve cells in the brain.

Paroxetine works by stopping the reabsorption of serotonin that is released from nerve cells in the brain.

This helps to prolong its effects and over time this helps to lighten the mood and relieve depression. Antidepressants like paroxetine are also effective in relieving anxiety symptoms, such as panic and fear.

Paroxetine will not change your personality or make you feel instantly happy and relaxed. It works over time to correct the chemical changes in your brain that have made you feel depressed or distressed, and make you feel like before.

How long does it take for the medicine to work?

It may take two to four weeks before the medicine starts to work, so it is very important that you continue to take it, even if it may not seem like much at first.

In general, you will need to continue taking paroxetine every day for several months. You should keep taking it for as long as your doctor tells you to.

If you feel that your depression or anxiety has worsened, or if you have distressing thoughts, or feelings about suicide or harm in the first few weeks, or indeed at any time during treatment or after stopping treatment, then it is very important to talk to your doctor

What should I know before taking paroxetine?

Selective serotonin reuptake inhibitor antidepressants, such as paroxetine, have rarely been associated with unpleasant or distressing restlessness and a feeling of having to move, often accompanied by an inability to sit or stand.

This is more likely to occur within the first few weeks of treatment if this will affect you. If you experience these symptoms, you should inform your doctor.

Paroxetine is not addictive. However, it is possible to have withdrawal symptoms such as dizziness, strange sensations, insomnia, intense dreams, sweating or anxiety when you stop taking it and for this reason your dose will be gradually reduced, usually over a few weeks or months, to avoid these problems when it’s time to stop treatment. Another anti-depression medicine is Deanxit. it is neither very dangerous nor addictive. This is because it is not a sedative, but an antidepressant.

Can I drink alcohol while taking the medicine?

Drinking alcohol in moderation while taking paroxetine shouldn’t cause problems for most people, although if you find that the medicine makes you feel tired or dizzy, then alcohol could make it worse.

However, it is generally recommended that you avoid drinking alcohol while taking antidepressants because alcohol can make depression worse. If you want to drink alcohol, you should ask your doctor if this is a good idea for you.

What about driving while taking paroxetine?

Paroxetine may reduce your ability to safely drive, operate machinery, ride a bicycle, or play sports.

For example, it can reduce your ability to make judgments or react to emergencies, and it can make some people feel tired or dizzy. Do not drive or operate machinery until you know how this medicine affects you and you are sure it will not affect your performance.

What brands are available?

Paroxetine is a generic drug. It is also available under the Seroxat brand.

Side effects of paroxetine

Side effects include dry mouth, nausea, dizziness, drowsiness, sexual dysfunction, and headache. Side effects generally occur during the first two weeks of treatment and are generally less severe and frequent than those seen with tricyclic antidepressants.

Paroxetine hydrochloride and mesylate are considered therapeutic alternatives to generic equivalents by the US Food and Drug Administration (FDA); both agents contain the same active moiety (ie, paroxetine), but are formulated as different salt forms.

Clinical studies establishing the efficacy of paroxetine under various conditions were conducted with paroxetine hydrochloride. Since both agents contain the same active moiety, the clinical efficacy of both agents is believed to be similar.

Paroxetine can be used to treat major depressive disorder (MDD), panic disorder with or without agoraphobia, obsessive compulsive disorder (OCD), social anxiety disorder (social phobia), generalized anxiety disorder (GAD), stress disorder posttraumatic disorder (PTSD)) and premenstrual dysphoric disorder (PMDD).

Paroxetine has the most evidence supporting its use for the anxiety-related disorders of selective serotonin reuptake inhibitors.

It has the highest anticholinergic activity of the agents in this class and compared to other selective serotonin reuptake inhibitors, paroxetine can cause increased weight gain, sexual dysfunction, sedation, and constipation .

Tell your doctor right away if you have serious side effects, including: tremors, restlessness, inability to keep still, decreased interest in sex, changes in sexual ability, numbness / tingling, easy bruising / bleeding, fast heartbeat / irregular, muscle weakness / spasm, seizures.

Management

Taking this medicine with food can decrease nausea. If this medicine makes you drowsy during the day, talk to your doctor about taking it at night.

The manufacturer recommends not chewing / crushing the tablet before taking it. However, many similar medications (immediate-release tablets) can be chewed / crushed.

It is important to continue taking this medicine even if you feel fine. Control weight and height in children taking this medicine. Before using this medicine, tell your doctor or pharmacist your medical history, especially of:

Personal or family history of bipolar / manic depressive disorder, personal or family history of suicide attempts, liver problems, kidney problems, seizures, low sodium in the blood, intestinal ulcers / bleeding (peptic ulcer disease), or bleeding problems , personal or family history of glaucoma .

Indications

Labeled indications include : major depressive disorder (MDD), panic disorder with or without agoraphobia, obsessive compulsive disorder (OCD), social anxiety disorder (social phobia), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD) ), and premenstrual dysphoric disorder (PMDD).

Unlabeled indications include : eating disorders, impulse control disorders, vasomotor symptoms of menopause, obsessive-compulsive disorder (OCD) in children, and agitation associated with mild dementia in non-psychotic individuals.

Pharmacodinámica

Paroxetine, an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) type, has no active metabolites and has the highest specificity for serotonin receptors of all the selective serotonin reuptake inhibitors.

~ 95% protein binding bound to plasma proteins.

It is used to treat depression resistant to other antidepressants, depression complicated by anxiety, panic disorder, social and general anxiety disorder, obsessive compulsive disorder (OCD), premenstrual dysphoric disorder, premature ejaculation and hot flashes of menopause in women with cancer of the mother .

In human platelets, paroxetine blocks the absorption of serotonin. It has weak effects on neuronal reuptake of norepinephrine and dopamine.

In vitro radioligand binding studies indicate that paroxetine has low affinity for muscarinic alpha1, alpha2, beta-adrenergic, dopamine (D2), 5-HT1, 5-HT2, and histamine (H1) receptors.

Mechanism of action

Paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake.

Paroxetine probably inhibits the reuptake of serotonin in the neuronal membrane, enhances serotonergic neurotransmission by reducing neurotransmitter turnover, thereby prolonging its activity at synaptic receptor sites, and potentiating 5-HT in the central nervous system.

Paroxetine is more potent than sertraline and fluoxetine in its ability to inhibit 5-HT reuptake.

Compared to tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) have dramatically reduced binding to histamine, acetylcholine, and norepinephrine receptors. The mechanism of action for the treatment of vasomotor symptoms is unknown.

Absorption

Paroxetine hydrochloride is slowly but completely absorbed after oral administration. Paroxetine mesylate salt is also completely absorbed after oral administration.

Oral bioavailability appears to be low due to extensive first-pass metabolism. Oral tablets and paroxetine hydrochloride suspension are reported to be bioequivalent. The absorption of either form of salt is not substantially affected by food.

Peak concentrations of Brisbelle (mesylate salt) were reached at 6 hours (range 3 to 8 hours). The steady state Cmax was 13.10 ng / mL. The AUC (area under the curve, after dosing) at steady state (0-ultimate) was 237 h * ng / mL.

Paroxetine mesylate generally follows nonlinear pharmacokinetics because CYP2D6, the enzyme that is responsible for the metabolism of paroxetine, is easily saturable.

Volume of distribution

Paroxetine is distributed throughout the body, including the central nervous system , with only 1% remaining in plasma.

Metabolism

Paroxetine is extensively metabolized after oral administration, probably in the liver. The main metabolites are polar and conjugated products of oxidation and methylation, which are easily eliminated by the body.

The predominant metabolites are glucuronic acid and sulfate conjugates. The metabolites of paroxetine do not possess significant pharmacological activity (less than 2% of that of the parent compound).

Paroxetine is metabolized by cytochrome P450 (CYP) 2D6. Enzyme saturation seems to account for the non-linear pharmacokinetics observed with increasing dose and duration of therapy.

Elimination route

Approximately 64% of a 30 mg oral solution of paroxetine was excreted in the urine with 2% as parent compound and 62% as metabolites.

Approximately 36% of the dose was excreted in the faeces (via bile), mainly as metabolites and less than 1% as the parent compound.

Toxicity

Symptoms of an overdose include: coma, dizziness, drowsiness, facial flushing, nausea, sweating, trembling, vomiting.

Side effects include: nervous system effects such as asthenia, drowsiness, dizziness, insomnia, tremor, and nervousness.

Gastrointestinal effects such as nausea, decreased appetite, constipation, diarrhea, and dry mouth; impotence, ejaculatory dysfunction (mainly ejaculatory delay) and other male genital disorders; female genital disorders (mainly anorgasmia or difficulty reaching climax / orgasm); and sweating.

Discontinuation syndrome can occur with abrupt withdrawal. Symptoms of discontinuation syndrome include flu-like symptoms, insomnia, nausea, imbalance, sensory changes, and hyperactivity.

Interactions of paroxetine with other medications

Some products that may interact with this drug include: thioridazine, other drugs that can cause bleeding / bruising (including antiplatelet drugs like clopidogrel, non-steroidal anti-inflammatory drugs like ibuprofen, ‘blood thinners’ like warfarin).

Examples of affected drugs include atomoxetine, phenothiazines, pimozide, risperidone, tamoxifen, tetrabenazine, antiarrhythmics like propafenone / flecainide, tricyclic antidepressants like desipramine / amitriptyline, among others.

Ask your pharmacologist about how to use these products safely.