Pharmacology Guide
Anti-Depressants
Last Updated:
Desipramine (Norpramine, Pertofrane) | Clomipramine (Anafranil) | Amitriptyline (Elavil) | Nortriptyline (Pamelor) | Buspirone (Buspar) | Escitalopram (Lexapro) | Venlafaxine (Effexor) | Fluvoxamine (Luvox) | Sibutramine (Meridia) | Paroxetine (Paxil) | Fluoxetine (Prozac) | Bupropion (Wellbutrin) | Sertraline (Zoloft)
Desipramine
| Norpramin, Pertofrane |
Mechanism of Action
|
Norpramin is used in the treatment of depression. It is one of a family of drugs called tricyclic antidepressants. Drugs in this class are thought to work by affecting the levels of the brain's natural chemical messengers (called neurotransmitters), and adjusting the brain's response to them. It has also been used to treat bulimia and attention deficit disorders, and to help with cocaine withdrawal. |
Therapeutic Use
|
Desipramine ( Norpramine, Pertofrane ) a antidepressants from the heterocyclic antidepressants family of drugs. This drug is used mainly in the treatment of endogenous depression but is also used to reduce the craving for cocaine. It may also be used to treat associated depression. May be used to treat chronic pain syndromes or attention deficit disorder in children over six. It may also be used to treat resistant malaria or reduce binge eating in patients with bulimia. |
Absorption
|
Desipramine is easily absorbed from the gastrointestinal tract following oral administration and is extensively bound to tissue and plasma proteins in the order of 90 to 95%. |
Metabolism
|
It is inactivated by hydroxylation and by further demethylation in the liver. Desipramine is excreted as a glucuronide largely in the urine (approximately 70%) and partly in the bile. |
Half-life
|
19-27 hours |
Average Daily Dose (adult)
|
100 to 200 mg . |
Adverse Effects
|
Blurred vision, constipation, drowsiness, dry mouth or low blood pressure. Other rare side effects can include: allergies, confusion, increased appetite, insomnia, racing heartbeat / palpitations, skin rashes, seizures, or sexual problems |
Drug Interaction
|
If Norpramin is taken with certain other drugs, the effects of either could be increased, decreased, or altered. It is especially important to check with your doctor before combining Norpramin with the following:
Cimetidine (Tagamet)
Drugs that improve breathing, such as Proventil
Drugs that relax certain muscles, such as Bentyl
Fluoxetine (Prozac)
Guanethidine (Ismelin)
Paroxetine (Paxil)
Sedatives/hypnotics (Halcion, Valium)
Sertraline (Zoloft)
Thyroid medications (Synthroid)
Extreme drowsiness and other potentially serious effects can result if Norpramin is combined with alcohol or other depressants, including narcotic painkillers such as Percocet and Demerol, sleeping medications such as Halcion and Nembutal, and tranquilizers such as Valium and Xanax. |
Contraindication
|
Serious, sometimes fatal, reactions have been known to occur when drugs such as Norpramin are taken with another type of antidepressant called an MAO inhibitor. Drugs in this category include Nardil and Parnate. Do not take Norpramin within two weeks of taking one of these drugs. Make sure your doctor and pharmacist know of all the medications you are taking. |
Clomipramine
| Anafranil |
Mechanism of Action
|
A tricyclic antidepressant that primarily inhibits serotonin reuptake. |
Therapeutic Use
|
Treatment of obsessive-compulsive disorder that causes distress and interferes with social and vocational activities. |
Absorption
|
Fairly well absorbed; reaches peak plasma levels in 2-6 hours after oral administration. |
Metabolism
|
Clomipramine is extensively biotransformed to desipramine and other metabolites by the P-450 enzymes. The metabolites are excreted as glucuronide conjugates. These metabolites are excreted in urine and feces. |
Half-life
|
19-37 hours |
Average Daily Dose (adult)
|
100-200 mg. |
Adverse Effects
|
Drowsiness, tremor, dizziness, headache, dry mouth, constipation and weight gain. |
Drug Interaction
|
The risks of using Anafranil in combination with other drugs have not been systematically evaluated. Given the primary CNS effects, caution is advised in using it concomitantly with other CNS-active drugs. |
Contraindication
|
Hypersensitivity to Anafranil or other tricyclic antidepressants. Should not be given in combination or within 14 days before or after treatment with a MAO inhibitor. |
Amitriptyline
|
Elavil |
Mechanism of Action
|
One of a group of tricyclic antidepressants whose action is believed to be related to its ability to block the reuptake of serotonin and norepinephrine which prolongs the action of these neurotransmitters. The exact mechanism of action is not known. |
Therapeutic Use
|
Depression and depression with anxiety and insomnia (disturbed sleep patterns). Also used with chronic pain due to cancer and other pain syndromes, including cluster and migraine headaches. Has been investigated for use with emotional lability (pathological laughing and crying) due to brain damage. Antidepressant effects may require 3 weeks before any benefit is observed. |
Absorption
|
Fairly well absorbed after oral administration. Peak blood levels are reached in 2-8 hours. |
Metabolism
|
Metabolized by N-demethylation and hydroxylation by P-450 enzymes. The hydroxylated form is conjugated. Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with little unchanged drug appearing in the urine. |
Half-life
|
31-46 hours. |
Average Daily Dose (adult)
|
75-150 mg |
Adverse Effects
|
Drowsiness, dry mouth, blurred vision, urinary retention, constipation, dizziness, cardiac palpitations or other arrhythmias,. High doses may cause seizures. |
Drug Interaction
|
It should not be given concomitantly with monoamine oxidase inhibitors. |
Contraindication
|
Sensitivity to the drug. Used with caution in patients with a history of seizures, urinary retention, angle-closure glaucoma or increased intraocular pressure. |
Nortriptyline
|
Pamelor |
Mechanism of Action
|
Another tricyclic antidepressant whose action is similar to amitriptyline, but fairly selective inhibitor of norepinephrine reuptake |
Therapeutic Use
|
Treatment of depression and chronic neurogenic (nerve tissue ) pain. |
Absorption
|
Fairly well absorbed, peak plasma level in 2-6 hours. |
Metabolism
|
Liver P-450 enzymes; oxidized metabolites excreted as conjugates. |
Half-life
|
18-44 hours. |
Average Daily Dose (adult)
|
75-150 mg. |
Adverse Effects
|
Hypotension, tachycardia, confusional states (especially in the elderly), numbness, tingling, dry mouth, skin rash, nausea and vomiting. |
Drug Interaction
|
Dangerous reaction can occur if combined with monoamine oxidase inhibitors. |
Contraindication
|
Monoamine oxidase inhibitors. Hypersensitivity to the drug. Contraindicated during the acute recovery period after myocardial infarction. |
Buspirone
|
Buspar |
Mechanism of Action
|
The mechanism of action of buspirone is unknown. Buspirone differs from typical benzodiazepine anxiolytics in that it does not exert anticonvulsant or muscle relaxant effects. It also lacks the prominent sedative effect that is associated with more typical anxiolytics. |
Therapeutic Use
|
Short-term symptomatic relief of excessive anxiety in patients with generalized anxiety disorder (psychoneurotic disorder). |
Absorption
|
Buspirone is rapidly and almost completely absorbed after oral administration. Peak plasma levels in 40 to 90 minutes after a single 20 mg dose. |
Metabolism
|
Buspirone is extensively metabolised in the liver. Metabolic sites in the liver are saturated by buspirone so that higher doses yield more unchanged buspirone. |
Half-life
|
2 to 3 hours |
Average Daily Dose (adult)
|
The recommended initial dose is 5 mg 2 to 3 times daily. |
Adverse Effects
|
Dizziness, headache, drowsiness, lightheadedness, insomnia, fatigue, nervousness, decreased concentration, excitement, depression, confusion, nightmares/vivid dreams, anger/hostility. Infrequently depersonalization, noise intolerance, euphoria/feeling high, dissociative reaction, fear, loss of interest, dysphoria, hallucinations, seizures, suicidal thoughts. Rarely, slurred speech, claustrophobia, cold intolerance, stupor, psychosis. |
Drug Interaction
|
Buspirone is highly bound to serum proteins and may displace other medicines. A slight increase (9%) has been noticed with digoxin. Similarly, buspirone possibly increased Cmax and AUC of nordiazepam by approximately 20%. Buspirone increases serum haloperidol concentration. Raised blood pressure has been noticed in patients taking both buspirone and MAO-inhibitors. Data from the controlled clinical trials with over 700 patients suggests safe co-administration of buspirone and analgesics, antihistamines, sedative-hypnotics, contraceptives, and antihypertensives. Diazepam, but not clorazepate, together with buspirone resulted in increased sedation. The concomitant use of CYP3A inhibitors increases buspirone bioavailability, e.g. itraconazole to 19-fold, erythromycin and diltiazem to 6-fold, verapamil to 3 fold. The concomitant use of these drugs with buspirone should be avoided or buspirone dose reduced accordingly.
Potent CYP enzyme inducers may decrease the bioavailability of buspirone. Rifampicin has decreased buspirone bioavailability to 10% from control values. |
Contraindication
|
Buspirone is contraindicated in patients with severe hepatic or severe renal impairment, patients with hypersensitivity to buspirone, myasthenia gravis, acute narrow-angle glaucoma, severe liver and kidney dysfunction, and/or pregnancy and breast-feeding. |
Escitalopram
|
Lexapro |
Mechanism of Action
|
Lexapro is an oral drug that is used for treating depression and generalized anxiety disorder. |
Therapeutic Use
|
Lexapro works by affecting neurotransmitters in the brain, the chemical messengers that nerves use to communicate with one another. Neurotransmitters are made and released by nerves and then travel to other nearby nerves where they attach to receptors on the nerves. Some neurotransmitters that are released do not bind to receptors and are taken up by the nerves that produced them. This is referred to as "reuptake."
Many experts believe that an imbalance of neurotransmitters is the cause of depression. Escitalopram prevents the reuptake of one neurotransmitter, serotonin, by nerves, an action which results in more serotonin in the brain to attach to receptors. Chemically, escitalopram is very similar to citalopram . Both are in the class of drugs called selective serotonin reuptake inhibitors (SSRIs), a class that also includes fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft). |
Absorption
|
Peak blood levels occur at about 5 hours. |
Metabolism
|
Escitalopram is metabolised in the liver to the demethylated and didemethylated metabolites. Alternatively, the nitrogen may be oxidised to form the N-oxide metabolite. Both parent and metabolites are partly excreted as glucuronides. Unchanged escitalopram is the predominant compound in plasma. After multiple dosing the mean concentrations of the demethyl and didemethyl metabolites are usually 28-31% and <5% of the escitalopram concentration, respectively. |
Half-life
|
27-32 hours. |
Average Daily Dose (adult)
|
10 mg . |
Adverse Effects
|
The most commonly-noted side effects associated with escitalopram are agitation or restlessness, blurred vision, diarrhea , difficulty sleeping, drowsiness, dry mouth, fever, frequent urination, headache , indigestion, nausea, increased or decreased appetite, increased sweating, sexual difficulties (decreased sexual ability or desire, ejaculatory delay), taste alterations, tremor (shaking), weight changes. Although changes in sexual desire, sexual performance and sexual satisfaction often occur as a result of depression itself, they also may be a consequence of the drugs used to treat depression. In particular, about one in 11 men given escitalopram report difficulties experiencing ejaculation. |
Drug Interaction
|
Citalopram (e.g., Celexa)—This medicine is very similar to escitalopram and should not be given at the same timeMonoamine oxidase (MAO) inhibitor activity (isocarboxazid [e.g., Marplan], phenelzine [e.g., Nardil], procarbazine [e.g., Matulane], selegiline [e.g., Eldepryl], tranylcypromine [e.g., Parnate])— Do not take escitalopram while you are taking or within 2 weeks of taking an MAO inhibitor. If you do, you may develop confusion, agitation, restlessness, stomach or intestinal symptoms, sudden high body temperature, extremely high blood pressure, severe convulsions, or the serotonin syndrome. At least 14 days should pass between stopping treatment with one medicine (escitalopram or the MAO inhibitor) and starting treatment with the other.
Sumatriptan (e.g., Imitrex)—Use with escitalopram may cause certain unwanted side effects and you should be watched by your doctor. |
Contraindication
|
The presence of other medical problems may affect the use of escitalopram. Make sure you tell your doctor if you have any other medical problems, especially:
- Diseases affecting metabolism or diseases involving blood circulation —caution should be used in patients with these medical problems
- Drug Abuse, history of— potential for increased dependence on medicine
- Kidney disease, severe— Until enough patients have been evaluated, caution is recommended for patients with severe kidney disease
- Liver disease—Higher blood levels of escitalopram may occur, increasing the chance of having unwanted effects. You may need to take a lower dose than a person without liver disease
- Mania or hypomania (history of)—Use of escitalopram may activate these conditions.
- Seizure disorders (history of)—The risk of having seizures may be increased.
|
Venlafaxine
|
Effexor |
Mechanism of Action
|
The mechanism of the antidepressant action of venlafaxine in humans is believed to be associated with its ability to inhibit neuronal serotonin and norepinephrine reuptake and its weak inhibition of dopamine reuptake. |
Therapeutic Use
|
Deoression. |
Absorption
|
Well absorbed. Food has no significant effect on absorption. |
Metabolism
|
Extensively metabolized in the liver by o-demethylation (P-450 enzymes). The o-desmethyl metabolite is active but is conjugated with glucuronic acid and excreted. |
Half-life
|
5 Hours. |
Average Daily Dose (adult)
|
75-150 mg |
Adverse Effects
|
Anxiety, insomnia (disturbed sleep patterns), anorexia, and sweating. |
Drug Interaction
|
Potential interactions with drugs metabolized by P-450 enzymes, e.g. diazepam, cimetidine, alcohol and haloperidol. |
Contraindication
|
Contraindicated in patients sensitive to the drug. Concomitant use in patients taking MAOIs is contraindicated. |
Fluvoxamine
|
Luvox |
Mechanism of Action
|
In common with the three better known SSRIs, fluoxetine, paroxetine and sertraline, fluvoxamine has a selective effect on the serotonin reuptake pump. 1 , 2 This causes an initial increase in serotonin only at the cell body and the dendrites, not at axon terminals (Fig. 1). The immediate consequence is to inhibit the rate of firing of serotonin neurons (and the release of serotonin) by an action at 5HT 1A somatodendritic autoreceptors. |
Therapeutic Use
|
Fluvoxamine is used to treat patients with obsessive-compulsive disorder and occasionally to treat depression. |
Absorption
|
Following a single 100 mg oral dose, peak plasma levels of 31 to 87 ng/mL were attained 1.5 to 8 hours post-dose. |
Metabolism
|
Fluvoxamine undergoes extensive hepatic transformation, mainly via oxidative demethylation, to at least 9 metabolites, which are excreted by the kidney. Ninety-four percent of an oral radioactive dose is recovered in the urine within 48 hours. The 2 major metabolites showed negligible pharmacological activity. In vitro binding of fluvoxamine to human plasma proteins is about 77% at drug concentrations up to 4000 ng/mL. |
Half-life
|
15.6 hours. |
Average Daily Dose (adult)
|
Treatment should be initiated at the lowest possible dose (50 mg) given once daily at bedtime, and then increased to 100 mg daily at bedtime after a few days, as tolerated. The effective daily dose usually lies between 100 and 200 mg, and should be adjusted gradually according to the individual response of the patient, up to a maximum of 300 mg. Dosage increases should be made in 50 mg increments. Doses above 150 mg should be divided so that a maximum of 150 mg is given in the bedtime dose. Tablets should be swallowed with water and without chewing. |
Adverse Effects
|
Side effects from fluvoxamine are common. Tell your doctor if any of these symptoms are severe or do not go away: drowsiness, dry mouth, upset stomach, headache, diarrhea, constipation, indigestion, nervousness, tremor, weakness, abnormal ejaculation, and/or difficulty sleeping. If you experience any of the following symptoms, call your doctor immediately:
- rapid heartbeat sweating skin rash hives
- seizures or convulsions
|
Drug Interaction
|
Tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially MAO inhibitors as phenelzine (Nardil) or tranylcypromine (Parnate) even if you stopped taking them in the last 2 weeks, alprazolam (Xanax), anticoagulants ('blood thinners') such as warfarin (Coumadin), astemizole (Hismanal), buspirone (Buspar), carbamazepine (Tegretol), cisapride (Propulsid), clozapine (Clozaril), cyclosporine, dextromethorphan, diazepam (Valium), diltiazem (Cardizem), diuretics ('water pill'), haloperidol (Haldol), heart medications, lithium, medications for depression, methadone, midazolam (Versed), phenytoin (Dilantin), pimozide (Orap), sumatriptan (Imitrex), terfenadine (Seldane), theophylline (TheoDur), thioridazine (Mellaril), triazolam (Halcion), L-tryptophan, and vitamins. |
Contraindication
|
Fluvoxamine should not be administered together with MAO inhibitors. At least 2 weeks should elapse after discontinuation of MAO inhibitor therapy before fluvoxamine treatment is initiated. MAO inhibitors should not be introduced within 2 weeks of cessation of therapy with fluvoxamine. |
Sibutramine
|
Meridia |
Mechanism of Action
|
It has been discovered that Sibutramine produces its therapeutic effects by inhibiting the reuptake of seratonin, norepinephrin and dopamine. It has two metabolites, DMS and DDMS . Both Sibutramine and it's metabolites are effective in vivo; however, in vitro Sibutramine is not effective. This is because the pharmacologically active substances are the metabolites, and in the in vitro studies, there is nothing to metabolise sibutramine, so it remains inactive. |
Therapeutic Use
|
Depression; obesity. |
Absorption
|
Sibutramine is rapidly absorbed from the gastro-intestinal tract and is first metabolised in the liver to DMS and DDMS. |
Metabolism
|
Sibutramine is primarily metabolised by the cytochrome P450(3A 4 ) enzyme. DMS and DDMS are also metabolised by the liver by hydroxylation and conjugation to pharmcologically inactive forms, which are then excreted from the body. The elimination half life of DMS is 16 hours and the elimination half-life of DDMS is 14 hours. |
Half-life
|
1.1 hours. Peak plasma concentrations of the metabolites are reached within 3-4 hours, and overall it has been determined that 77% of a single dose of sibutramine is absorbed by the body. |
Average Daily Dose (adult)
|
10 mg. |
Adverse Effects
|
Side effects of Sibutramine include dry mouth, constipation and insomnia. Less common side effects include headache, increased sweating, increased blood pressure and increased heart rate. Of these, the issue of increased blood pressure is the most concerning. |
Drug Interaction
|
Sibutramine is incompatible with the following drugs (Information from 28 Medline Plus ):
- Appetite suppressants, (benzphetamine [e.g., Didrex], diethylpropion [e.g., Tenuate], mazindol [e.g., Sanorex], phendimetrazine [e.g., Phendiet], phentermine [e.g., Ionamin])—The effects of using sibutramine in combination with another appetite suppressant are not known. Bromocriptine (e.g., Parlodel) Buspirone (e.g., BuSpar) Certain tricyclic antidepressants (amitriptyline [e.g., Elavil], clomipramine [e.g., Anafranil], imipramine [e.g., Tofranil]) Dextromethorphan (cough medicine) Levodopa (e.g., Sinemet) Lithium (e.g., Eskalith) Meperidine (e.g., Demerol) Nefazodone (e.g., Serzone) Pentazocine (e.g., Talwin) Selective serotonin reuptake inhibitors (citalopram [e.g., Celexa], fluoxetine [e.g., Prozac], fluvoxamine [e.g., Luvox], paroxetine [e.g., Paxil], sertraline [e.g., Zoloft]) Street drugs (LSD, MDMA [e.g., ecstasy], marijuana) Sumatriptan (e.g., Imitrex) Tramadol (e.g., Ultram) Trazodone (e.g., Desyrel) Tryptophan Venlafaxine (e.g., Effexor)—Using these medicines with sibutramine may increase the chance of developing a rare, but very serious, unwanted effect known as the serotonin syndrome. Symptoms of this syndrome include confusion, diarrhea, fever, poor coordination, restlessness, shivering, sweating, talking or acting with excitement you cannot control, trembling or shaking, or twitching. Moclobemide (e.g., Manerex)—Taking moclobemide and sibutramine together or less than 3 days apart may increase the chance of developing serious unwanted effects, including the serotonin syndrome.
- Monoamine oxidase (MAO) inhibitors (furazolidone [e.g., Furoxone], phenelzine [e.g., Nardil], procarbazine [e.g., Matulane], selegiline [e.g., Eldepryl], tranylcypromine [e.g., Parnate]). This combination in particular has been shown to considerably increase the likelihood of developing the serotonin syndrome
|
Contraindication
|
Sibutramine should not be prescribed for people with a history of coronary artery disease, congestive heart failure, arrhythmias or stroke, as it may dangerously increase the individual's heart rate and/or blood pressure. |
Paroxetine
|
Paxil |
Mechanism of Action
|
Paroxetine HCl is an orally administered antidepressant with a chemical structure unrelated to other selective serotonin reuptake inhibitors or to tricyclic, tetracyclic or other available antidepressant agents.
Paroxetine is a potent and selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor (SSRI). This activity of the drug on brain neurons is thought to be responsible for its antidepressant effects.
|
Therapeutic Use
|
Paroxetine (Paxil) is used to treat depression, obsessive-compulsive disorders, panic attacks, social anxiety disorder, generalized anxiety disorder, and posttraumatic stress disorder. Paroxetine controlled-release (Paxil CR) is used to treat depression and panic attacks. Paroxetine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amounts of certain natural substances in the brain. |
Absorption
|
Peak plasma levels generally occurred within 3 to 7 hours. |
Metabolism
|
Paroxetine is subject to a biphasic process of metabolic elimination which involves presystemic (first-pass) and systemic pathways. First-pass metabolism is extensive, but may be partially saturable, accounting for the increased bioavailability observed with multiple dosing. The majority of the dose appears to be oxidized to a catechol intermediate which is converted to highly polar glucuronide and sulfate metabolites through methylation and conjugation reactions. The glucuronide and sulfate conjugates of paroxetine are about >10000 and 3000 times less potent, respectively, than the parent compound as inhibitors of 5-HT reuptake in rat brain synaptosomes. Approximately 64% of an administered dose of paroxetine is eliminated by the kidneys and 36% in the feces. Less than 2% of the dose is recovered in the form of the parent compound. |
Half-life
|
24 hours. |
Average Daily Dose (adult)
|
The administration of paroxetine should be initiated at 20 mg daily. For most patients, 20 mg daily will also be the optimum dose. The therapeutic response may be delayed until the third or fourth week of treatment. |
Adverse Effects
|
Side effects from paroxetine are common, and include upset stomach, drowsiness, weakness or tiredness, excitement or anxiety, insomnia, nightmares, dry mouth, changes in appetite or weight. Tell your doctor if any of these symptoms are severe or do not go away, especially constipation, difficulty urinating, frequent urination, blurred vision, changes in sex drive or ability, excessive sweating. If you experience any of the following symptoms, call your doctor immediately:
- jaw, neck, and back muscle spasms slow or difficult speech shuffling walk persistent fine tremor or inability to sit still fever, chills, sore throat, or flu-like symptoms difficulty breathing or swallowing severe skin rash yellowing of the skin or eyes
- irregular heartbeat
|
Drug Interaction
|
Tell your doctor and pharmacist what prescription and nonprescription drugs you are taking or have taken within the last 2 weeks, especially anticoagulants [warfarin (Coumadin)]; antidepressants; antihistamines; cimetidine (Tagamet); digoxin (Lanoxin); levodopa (Sinemet, Larodopa); lithium (Eskalith, Lithobid); MAO inhibitors [phenelzine (Nardil), tranylcypromine (Parnate)]; medication for high blood pressure, seizures, Parkinson's disease, asthma, colds, or allergies; muscle relaxants; phenobarbital; procyclidine (Kemadrin); sedatives; sleeping pills; sumatriptan (Imitrex); theophylline (Theo-Dur); thioridazine (Mellaril); thyroid medications; tranquilizers; tryptophan; and vitamins. |
Contraindication
|
Paroxetine is contraindicated in patients who are known to be hypersensitive to the drug.
Paroxetine should not be used in combination with MAO inhibitors or within 2 weeks of terminating treatment with MAO inhibitors. Treatment with paroxetine should then be initiated cautiously and dosage increased gradually until optimal response is reached. MAO inhibitors should not be introduced within 2 weeks of cessation of therapy with paroxetine. |
Fluoxetine
|
Prozac |
Mechanism of Action
|
Fluoxetine is one of the selective serotonin reuptake inhibitors (SSRIs). Its beneficial effects are believed to be related to this effect. |
Therapeutic Use
|
Depression; obsessive compulsive disorders; and bulimia. |
Absorption
|
Well absorbed from GI tract independent of presence of food. Peak plasma levels observed after 6 to 8 hours. |
Metabolism
|
Extensively in the liver, by P-450 enzymes; active metabolite. Has a long half-life. |
Half-life
|
7-9 days. |
Average Daily Dose (adult)
|
20-40 mg |
Adverse Effects
|
Insomnia, (disturbed sleep patterns), anxiety, nervousness, dizziness, fatigue, gastrointestinal disturbance, nausea. |
Drug Interaction
|
Should not be used with MAO inhibitors; prolongs the half-life and increases blood levels of other drugs metabolized by P-450 enzymes such as benzodiazepines. |
Contraindication
|
Known hypersensitivity to the drug, and MAO inhibitors are contraindicated. |
Bupropion
|
Wellbutrin |
Mechanism of Action
|
The neurochemical mechanism of the antidepressant effect of bupropion is not known. Bupropion does not inhibit monoamine oxidase. Compared to classical tricyclic antidepressants, it is a weak blocker of the neuronal uptake of serotonin and norepinephrine; it also inhibits the neuronal re-uptake of dopamine to some extent.
Bupropion produces dose-related CNS stimulant effects in animals, as evidenced by increased locomotor activity, increased rates of responding in various schedule-controlled operant behavior tasks, and, at high doses, induction of mild stereotyped behavior. |
Therapeutic Use
|
Bupropion is used to treat people with depression and to aid in smoking cessation treatment. |
Absorption
|
Peak plasma bupropion concentrations are usually achieved within 2 hours, followed by a biphasic decline. |
Metabolism
|
Several of the known metabolites of bupropion are pharmacologically active, but their potency and toxicity relative to bupropion have not been fully characterized. However, because of their longer elimination half-lives, the plasma concentrations of at least two of the known metabolites can be expected, especially in chronic use, to be very much higher than the plasma concentration of bupropion. This is of potential clinical importance because factors or conditions altering metabolic capacity (e.g., liver disease, congestive heart failure, age, concomitant medications, etc.) or elimination may be expected to influence the degree and extend of accumulation of these active metabolites. |
Half-life
|
The average half-life of the second (post-distributional) phase is approximately 14 hours, with a range of 8 to 24 hours. Six hours after a single dose, plasma bupropion concentrations are approximately 30% of peak concentrations. Plasma bupropion concentrations are dose-proportional following single doses of 100 to 250 mg; however, it is not known if the proportionality between dose and plasma level is maintained in chronic use. |
Average Daily Dose (adult)
|
75 mg. |
Adverse Effects
|
Adverse events commonly encountered in patients treated with bupropion are agitation, dry mouth, insomnia, headache/migraine, nausea/vomiting, constipation, and tremor. |
Drug Interaction
|
Drugs that lower seizure threshold, e.g.: Antipsychotics* Antidepressants* Antimalarials Tramadol Theophylline Systemic steroids Sedating antihistamines, Quinolones; Diabetic patients treated with hypoglycamics or insulin; betablockers, and MAOIs. |
Contraindication
|
Bupropion is contraindicated in patients with a seizure disorder. Bupropion is also contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa because of a higher incidence of seizures noted in such patients treated with bupropion. The concurrent administration of bupropion and a monoamine oxidase (MAO) inhibitor is contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with bupropion. Bupropion is contraindicated in patients who have shown an allergic response to it. |
Sertraline
|
Zoloft |
Mechanism of Action
|
Inhibits neuronal uptake of serotonin. In this regard it is classified as a selective serotonin reuptake inhibitor (SSRI). |
Therapeutic Use
|
Treatment of depression, obsessive-compulsive disorders and panic disorders. |
Absorption
|
Fairly well absorbed. Peak plasma level reached 4-8 h after a single dose. |
Metabolism
|
The principle initial pathway of metabolism for sertraline is N-demethylation by P-450 system. |
Half-life
|
26 hours |
Average Daily Dose (adult)
|
100-150 mg |
Adverse Effects
|
Headache, insomnia (disturbed sleep patterns), agitation, anxiety, dizziness, nausea. |
Drug Interaction
|
Potential effects of coadministration of drugs highly metabolized by P-450 enzymes. |
Contraindication
|
Concomitant use in patients taking monoamine oxidase inhibitors. |
These brief pharmaceutical summaries do not include all information important for patient use and should not be used as a substitute for professional medical advice. Consult the prescribing doctor and read package inserts before using these or any other medications or supplements.
CDER
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
National Institutes of Health
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