Drug Treatment Of Depression

Several classes of drugs and medications can be used to treat depression: Selective serotonin reuptake inhibitors (SSRIs) Serotonin modulators (5-HT2 blockers) Selective serotonin-norepinephrine reuptake inhibitor norepinephrine dopamine reuptake inhibitor Heterocyclic antidepressants Monoamine oxidase inhibitors (MAOIs) Melatonerges antidepressant Drug Selection Can the earlier response geared to a particular antidepressant. Otherwise, SSRIs are often the initial drug of choice. The various SSRIs are indeed in typical cases of comparable effectiveness, but due to certain drug properties more or less suitable for certain patients (antidepressants). Selective serotonin reuptake inhibitors (SSRIs) These drugs inhibit the reuptake of serotonin (5-hydroxytryptamine [5-HT]). Among the SSRIs are citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and Vilazodone. Although these drugs have the same mechanism of action, but they must be specifically selected because of their different clinical characteristics. SSRIs have a wide therapeutic range, are relatively easy to administer and often require dose adjustment (except fluvoxamine). By inhibition of reuptake of 5-HT in the presynaptic 5-HT is more for the stimulation of post-synaptic 5-HT receptors are available. SSRI act selectively on the 5-HT system, but not specifically to the various 5-HT receptors. They stimulate with antidepressant and anxiolytic effects, the 5-HT1 receptors and the 5-HT2 receptors, which often leads to anxiety, insomnia and sexual dysfunction, as well as the 5-HT 3 receptors, which usually causes nausea and headaches. Therefore, SSRIs can paradoxically fear suppress as well as cause. Some patients may appear agitated, more depressed and anxious within a week after the start of SSRI treatment or after a dose increase. Patients and their families should be informed of this possible consequence and advised to seek medical attention if your symptoms worsen with treatment. This situation should be carefully monitored as some patients v. a. increases in younger children and adolescents, the risk of suicide if agitation, increased depressive symptoms and anxiety not detected and treated quickly. Several analyzes of the FDA database of industry-sponsored studies led to a side effect warning that antidepressants are usually associated with an increased risk in the occurrence of suicidal thoughts and suicide attempts in patients ? 24 year age. Subsequent analyzes of the FDA and other data cast doubt on this conclusion (1). Sexual dysfunction (insesondere orgasm difficulties as well as decreased libido and erectile dysfunction) occur at least one-third of patients. Some SSRIs cause weight gain. Others, v. a. Fluoxetine may result in the first months of appetite. SSRIs have little anticholinergic, adrenolytic and cardiac side effects. Sedation rarely or never comes before, but can daytime sleepiness occur in the first weeks of treatment in some patients. In some patients, there is also loose stool or diarrhea. Drug interactions are relatively rare; However, fluoxetine, paroxetine and fluvoxamine may inhibit the cytochrome P-450 (CYP450) isoenzymes, which can cause serious drug interactions. These medicines such can. As the metabolism of certain beta blockers, incl. Propranolol and metoprolol inhibit, and thus lead to hypotension and bradycardia. Withdrawal symptoms (. Eg, irritability, anxiety, nausea) may occur when the drug is abruptly discontinued; fluoxetine, such effects are less likely. Reference of selective serotonin reuptake inhibitors (SSRIs) 1. Gibbons RD, Brown CH, Hur K, et al: Suicidal thoughts and behavior with antidepressant treatment: Reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. Arch Gen Psychiatry 69 (6): 580-587, 2012. Clarification and additional information. Arch Gen Psychiatry 70 (8): 881, 2013. serotonin modulators (5-HT 2 blockers) These drugs block mainly the 5-HT2 receptor and inhibit the reuptake of 5-HT and noradrenaline. Serotonin modulators include Trazodone, mirtazapine serotonin modulators have antidepressant and anxiolytic effects, but do not cause sexual dysfunction. Trazodone does not inhibit the reuptake of 5-HT in the presynaptic terminal. It has caused priapism (1/1000 patients) and can lead as noradrenergic alpha-1 blockers orthostatic hypotension. It has a strong sedative, which is why its use in antidepressant doses (> 200 mg / day) is limited. Usually it is administered in doses of 50-100 mg at bedtime in depressed patients with insomnia. Mirtazapine inhibits the 5-HT-Wiederauafnahme and blocking the alpha-2-adrenergic autoreceptors as well as 5-HT2 and 5-HT3 receptors. Thus, the serotonergic and noradrenergic function without sexual dysfunction or nausea are amplified. It has no cardiac side effects, minimal interactions with drug metabolizing liver enzymes and is generally well tolerated, but it acts through H1 (histamine) blockade sedating and causes weight gain. Selective serotonin-norepinephrine reuptake inhibitor, these drugs (eg. B. desvenlafaxine, duloxetine Levomilnacipran, Venlafaxine, vortioxetine) similar to tricyclic antidepressants have a dual mechanism of action to 5-HT and noradrenaline. However, its toxicity is approximately equal to that of SSRIs. Nausea is the most common problem in the first 2 weeks; moderate dose-related increases in blood pressure occur at high doses. A sudden discontinuation of the drug often leads to withdrawal symptoms (eg. As irritability, anxiety, nausea). Duloxetine is comparable in terms of efficacy and adverse effects of venlafaxine. Norepinephrine-dopamine reuptake inhibitor By far not clearly understood mechanisms affect these drugs mostly catecholaminergic, dopaminergic and noradrenergic functions. They have no effect on the 5-HT system. Bupropion is currently the only drug in this class. It can help depressed patients with co-existing attention deficit hyperactivity disorder or cocaine dependency and is used for smoking cessation. Bupropion can cause hypertension in individual cases, but has no other cardiovascular effects. Bupropion may be 3 times daily in 0.4% of patients with doses> 150 mg (or in sustained-release> 200 mg SR 2 times daily or> 450 mg XR 1 time daily) induce seizures; the risk is elevated in bulimic patients. Bupropion does not cause sexual dysfunction and has little interaction with other drugs, but it inhibits the cytochrome isoenzyme CYP2D6 in the liver. Agitation as a common side effect can weaken considerably by sustained-release (SR or XR). Heterocycles antidepressants These drugs group which was previously used as a standard treatment includes, tricyclic (the tertiary amines amitriptyline and imipramine, and its secondary amine metabolites nortriptyline and desipramine), modified tricyclic and tetracyclic antidepressants. However, heterocyclic antidepressants increase the availability of norepinephrine and, to a certain degree by inhibiting the reuptake in the synaptic cleft of 5-HT. The long-term use leads to the down-regulation of alpha-1-adrenergic receptors on the postsynaptic membrane-a possible final common pathway of their antidepressant activity. Despite their effectiveness, these drugs are now used infrequently because they are toxic in overdose and more adverse effects than other antidepressants. The common adverse effects of Heterozyklika based on their blockade of muscarinic and histamine receptors and their alpha-1-adrenolytic action. Many Heterozyklika have strong anticholinergic properties and are therefore unsuitable for elderly patients and for patients with benign prostatic hyperplasia, glaucoma or chronic constipation. All Heterozyklika, v. a. Maprotiline and clomipramine, decrease the seizure threshold. Monoamine oxidase inhibitors (MAOIs) These drugs inhibit the oxidative deamination of the 3 classes of biogenic amines (noradrenaline, dopamine, 5-HT) and other phenylethylamines. Its primary benefit is the treatment of refractory or atypical depression when SSRIs, tricyclic antidepressants and sometimes electroconvulsive therapy are ineffective. The MAOIs marketed as antidepressants in the US (z. B. phenelzine [n. D. Übers .: not available in Germany], tranylcypromine, isocarboxazid [n. D. Übers .: not available in Germany]) are irreversible and non-selective ( and inhibit both MAO-A and MAO-B). One other MAOIs (selegiline), which only inhibits the MAO-B at lower doses, is available as a patch. Einehypertensive crisis can occur if MAO inhibitors, MAO-A and MAO-B inhibiting simultaneously contain a sympathomimetic or foods containing tyramine or dopamine to be taken. This effect is called the Cheese effect as mature cheese has a high tyramine content. MAOIs are of concern because this reaction rarely used. The lower dose of selegiline patch applies regardless of specific dietary restrictions as safe, unless the dose must be higher than the starting level (6 mg patches). Selective and reversible MAOI (eg. As moclobemide, befloxatone), which only inhibit MAO-A, are relatively free of these interactions, but not available in the US. To avoid hypertensive and febrile crises should patients taking MAOIs, the following medicines, foods and beverages to avoid: sympathomimetic (. Eg, pseudoephedrine), dextromethorphan, reserpine and meperidine [Note. d. Übers .: in Germany not available]; Malt beer, red wine, sherry, liqueurs and overripe or ripened foods that tyramine or dopamine containing (eg. As beans, yeast extracts, pickled figs, raisins, yogurt, cheese, sour cream, soy sauce, pickled herring, caviar, liver, banana peels, meat with lots tenderizers). Patients should perform 25 mg tablets chlorpromazine with it, of which 1-2 tablets should be taken at the first sign of hypertensive reaction, and then seek as soon as possible the nearest emergency room. Common adverse effects include erectile dysfunction (least often in tranylcypromine), anxiety, nausea, dizziness, insomnia, Fußödeme and weight gain. MAOIs should not be used in conjunction with antidepressants from other classes; between the intake of antidepressants of various classes should lie (5 weeks at fluoxetine because of the long half-life) for at least 2 weeks. Co-administration of MAOIs and antidepressants which affect the 5-HT system (z. B. SSRI) may cause a malignant Neuroleptokasyndrom (malignant hyperthermia, muscle, kidney failure, seizures or death failure). Patients taking MAOIs while maintaining anti-asthmatics, anti-allergic agents, a local anesthetic or a general anesthetic, should be treated by a psychiatrist and an internist, a dentist or an anesthesiologist with experience in Neuropsychopharmacology. Melatonerges antidepressant agomelatine is a melatonergic (MT1 / MT2) Agoniste and a 5-HT 2C receptor antagonist. It is used for major depressive episodes. Agomelatine has fewer side effects than most antidepressants and causes daytime no sedation, no insomnia, weight gain or sexual dysfunction. It is not addictive and does not cause withdrawal symptoms. It can cause headaches, nausea and diarrhea. It can also lead to elevated liver enzymes, and these values ??should be measured at baseline and then every 6 weeks. It is contraindicated in patients with hepatic dysfunction. Agomelatine is taken at bedtime in a dosage of 25 mg. Drug selection and administration of the drug selection can be based on previous response to a given antidepressant. Otherwise, SSRIs are often the initial drug of choice. Although the various SSRIs are typical cases of comparable effectiveness, but due to certain drug properties for certain patients more or less suitable (see table: antidepressants). Antidepressants drug dose * therapeutic dose range precautions SSRI Causes withdrawal symptoms with abrupt withdrawal (less likely with fluoxetine) citalopram 20 mg 1 time daily. 20-40 mg Lower potential for drug-drug interactions, since lower impact on CYP450 isoenzymes risk of QT interval prolongation which limits the doses at ? 40 mg / day Escitalopram 10 mg 1 times daily 10-20 mg Lower potential for drug-drug interactions, since lower impact on CYP450 isoenzymes fluoxetine 10 mg 1 times daily 20-60 mg very long half-life Causes less likely Withdrawal The only antidepressant with nachgewiesenener effectiveness in children fluvoxamine 50 mg 1 times daily 100-200 mg Can a clinically significant increase in blood levels of Theop hyllin, warfarin and cause clozapine has for interactions between its active metabolites and HCA, carbamazepine, antipsychotics or IC antiarrhythmic If a CYP450 profile similar to fluoxetine, paroxetine 20 mg 1 time daily potential. 25 mg once daily 20-50 mg CR 25 -62.5 mg CR Has potential for interactions between its active metabolites and HCA, carbamazepine, antipsychotics or IC antiarrhythmic If a CYP450 profile similar to fluoxetine Can among the SSRIs the highest weight gain cause sertraline 50 mg 1 times daily 50-200 Has under mg the SSRI the highest incidence of loose stool vilazodone 10 mg p.o. 1 time / day for 7 days, then increase to 20 mg daily for 7 days 10 to 40 mg (titrated from 5 to 10 mg every 7 days) can increase the risk of bleeding when the drug with aspirin, taken other NSAIDs or other drugs is that should influence the coagulation not be stopped abruptly; the dose should be gradually reduced serotonin modulators (5-HT2 blockers) mirtazapine 15 mg of 1-times daily 15-45 mg causing weight gain, and sedation has fewer sexual side effects as SSRIs and serotonin-norepinephrine reuptake inhibitor Trazodone 50 mg 3 times / day 150 -300 mg Can May cause priapism orthostatic hypotension cause selective serotonin norepinephrine Resume ahmehemmer causing withdrawal symptoms upon abrupt cessation Desvenlafaxine 50 mg 1 time per day 50-100 mg Can blood pressure or HF increase (control of blood pressure before the start of drug administration and monitoring of blood pressure and HF while patients are taking the drug) Duloxetine 20 mg of 2- times daily. 60-120 mg dose dependent moderate increase in systolic and diastolic blood pressure can cause urinary retention slight less potential for drug-drug interactions in men because of reduced impacts on CYP450 isoenzymes Levomilnacipran 20 mg 1 time / day for 2 days, then 40 mg increase 40-120 mg (dose in increments of 40 mg / day in intervals of ? 2 Days 1 times / day; 120 mg / day does not exceed) Can blood pressure or HF increase (control of blood pressure before the start of drug administration and monitoring of blood pressure and RF while patients are taking the drug) may increase risk of bleeding (caution when the drug with aspirin, other is taken NSAIDs or anticoagulants) Can urinary retention or retention effect (caution in patients with obstructive disorders of the urinary tract and the medication must be stopped if symptoms develop) venlafaxine 25 mg 3 times / day 37.5 mg once daily XR 75-375 mg 72-225 mg dose-dependent XR modest increase in diastolic blood pressure Dual effect of noradrenaline and 5-HT reuptake in ca (Not dose-dependent) Should be tapered slowly at weaning less potential for drug-drug interactions, since lower impact on CYP450 isoenzymes vortioxetine 5-10 mg 10-20 mg Patients should one times daily warned. 150 mg Rarely increase in systolic blood pressure before an increased bleeding risk be, when the drug with aspirin or other NSAIDs, or other medication is taken, which influence the coagulation or bleeding norepinephrine-dopamine reuptake inhibitor bupropion 100 mg of 2 times / day 150 mg once daily SR 150 mg once XL daily 200-450 mg contraindicated in patients with bulimia or with seizure inclination Can with HCA interact, increasing the risk of seizures increases can dose-dependent short-term memory loss cause Heterozyklika contraindicated in patients with coronary heart disease, certain arrhythmias, narrow-angle glaucoma, benign prostatic hyperplasia, or esophageal hiatal hernia can cause orthostatic hypotension, which leads to falls and fractures, increase the effects of alcohol and increase the blood levels of antipsychotics in substantial overdose potentially lethal effect amitriptyline 50 mg 1 time daily 150-300 mg Causes weight gain amoxapine 50 mg 2 times / day 150-400 mg Can extrapyramidal side effects clomipramine 25 mg 1 times daily 100-250 mg lowers the seizure threshold in doses> 250 mg / day desipramine 25 mg 1 time daily 150-300 mg – Doxepin 25 mg 1 times daily 150-300 mg Causes weight gain imipramine 25 mg 1 times daily 150-300 mg can cause excessive sweating and nightmares maprotiline 75 mg 1 times daily 150-225 mg Increased risk of seizures with rapid dose escalation at high doses nortriptyline 25 mg 1 time a day 50-150 mg rms within the therapeutic window protriptyline 5 mg 3 times / day 15-60 mg long half-life (74 h) trimipramine 50 mg of 1-times daily 150-300 mg causes weight gain MAOH central serotonin syndrome possible when taken together with an SSRI , 10 mg Causes hypertensive crisis possible if ingested along with other antidepressants, sympathomimetic or other selective drugs or eating certain foods and drinks in substantial overdose potentially lethal effect isocarboxazid 2 times a day 30-60 mg orthostatic hypotension phenelzine 15 mg 3 times / day 45-90 mg Causes orthostatic hypotension selegiline transdermal 6 mg 1 time a day 12 mg Can reactions at the application site and insomnia cause tranylcypromine 10 mg 2 times Causes 30-60 mg daily orthostatic hypotension has amphetamine-like stimulant effects and a moderate potential for abuse Melatonerges antidepressant agomelatine (5-HT 2C receptor antagonist) 25 mg 1 time / day before the bedtime 25-50 mg should be stopped immediately if symptoms or signs of potential damage to the develop liver, or when increase serum transaminases to> 3 times the upper limit of normal * All medications are given orally, with the exception of transdermal selegiline. CR = release at a constant speed; CYP450 = cytochrome P-450 system; HCA = heterocyclic antidepressants; HR = heart rate; 5-HT = 5-hydroxytryptamine (serotonin), MAOIs = monoamine oxidase inhibitors; SR = release at a decreasing rate; XL = sustained release; XR = sustained release. The invalidity of an SSRI, it can be replaced with another SSRI, or an antidepressant from a different class can be used instead. Tranylcypromine (20-30 mg p.o. 2 times / day) is in refractory depression after successive attempts at treatment with other antidepressants often effective; it should be administered by a doctor who has experience with the use of MAOIs has. The psychological support of patients and is especially important in refractory cases. Insomnia is a common side effect of SSRIs and is treated by dose reduction or the additional administration of low-dose trazodone or another sedating antidepressant. Initial nausea and loose stools usually go back quickly, throbbing headache, however not lie down forever, so then a change to another class of substances is necessary. An SSRI should be discontinued if it causes agitation. With decreasing libido, impotence or orgasmic dysfunction during a SSRI therapy dose reduction can help or switching to a serotonin modulator or a norepinephrine-dopamine reuptake inhibitor. SSRIs have a more drive-increasing effect and should be administered in the morning. If the total dose of the heterocyclic antidepressant taken at bedtime, sedatives are mostly unnecessary, undesirable effects during the day will be minimized and the adherence is improved. To avoid excessive stimulation, MAOIs are usually given in the morning and early afternoon. With a therapeutic response to most of antidepressants is usually expected within 2-3 weeks (sometimes after 4 days or after 8 weeks). In the first episode of a mild to moderate depression, the antidepressant should be given for 6 months and then gradually tapered off over 2 months. In a severe episode, a relapse or at risk of suicide completely antidepressant dose is continued as a maintenance dose. In a psychotic depression, the combination of an antidepressant with antipsychotic is more effective than any anewendet individually. Patients who have recovered from a psychotic depression, have had a higher risk of relapse than those a non-psychotic depression, so a prophylactic treatment is particularly important. To avoid recurrences i. Gen. eine durchgehende Behandlung mit Antidepressiva über 6–12 Monate (bei > 50-jährigen Patienten bis zu 2 Jahre) erforderlich. Die meisten Antidepressiva, insbesondere SSRI, sollten ausgeschlichen und nicht abrupt abgesetzt werden (durch Dosisreduktion um ca. 25% pro Woche); abruptes Absetzen von SSRI kann ein sog. Absetzsyndrom (Übelkeit, Frösteln, Muskelschmerzen, Schwindel, Angst, Reizbarkeit, Schlaflosigkeit, Müdigkeit) hervorrufen. Wahrscheinlichkeit und Schwere des Entzugs variieren invers mit der Halbwertszeit des SSRI.

Health Life Media Team

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