Antidepressants escitalopram

Single-enantiomer technology— which earned its developers the Nobel Prize in Chemistry in 2000—enables the production of commercial quantities of medications that contain only the desired enantiomer, the other having been removed in the production process. Such is the case, for example, in the antidepressant escitalopram (trade name Lexapro) (see Figure B.3). This drug is the successor of citalopram (trade... 

Baumann P, Zullino DF, Eap CB. Enantiomers potential in psychopharmacology—a critical analysis with special emphasis on the antidepressant escitalopram. Europ Neuro-psychopharmcol 2002 12 433—444... 

Drug-drug interactions SSRIs Aripiprazole had no effects on the pharmacokinetics of escitalopram, fluoxetine, paroxetine, sertraline, or venlafaxine either in healthy subjects ( =63) or in patients with major depressive disorder ( =498) [69. Point estimates for mean plasma concentration ratios indicated no substantial effect of aripiprazole on any antidepressant escitalopram 0.97 (0.91-1.03), fluoxetine 1.18 (1.05-1.32), paroxetine 0.73 (0.60-0.89), sertraline 0.96 (0.89-1.04), or venlafaxine 0.97 (0.89-1.05). 

After more than a decade of use, bupropion (24) is considered a safe and effective antidepressant, suitable for use as first-line treatment. In addition, it is approved for smoking cessation and seasonal affective disorder. It is also prescribed off-label to treat the sexual dysfunction induced by SSRIs. Bupropion is often referred to as an atypical antidepressant and has much lower affinity for the monoamine transporters compared with other monoamine reuptake inhibitors. The mechanism of action of bupropion is still uncertain but may be related to inhibition of dopamine and norepinephrine reuptake transporters as a result of active metabolites [71,72]. In a recently reported clinical trial, bupropion extended release (XL) had a sexual tolerability profile significantly better than that of escitalopram with similar re-... 

SSRls and SNRIs. The SSRl antidepressants, together with venlafaxine, have replaced the benzodiazepines as treatments of choice for GAD. Paroxetine and escitalopram are FDA approved for GAD, though it is generally believed that all SSRls and SNRIs are effective for GAD. Similar to the TCAs, SSRIs/SNRIs appear to be most effective for the intrapsychic symptoms of GAD but less effective than benzodiazepines for the somatic manifestations of the disorder. 

SSRls. SSRI antidepressants have also received considerable scrutiny in the treatment of OCD. Fluoxetine, fluvoxamine, paroxetine, and sertraline are all approved by the FDA for the treatment of OCD. Current studies suggest that each of these medications is more effective for OCD when administered at the higher end of the therapeutic dose range, that is, fluoxetine 60-80 mg/day, fluvoxamine 200-300 mg/ day, paroxetine 40-60 mg/day, and sertraline 150-200 mg/day. No controlled studies are yet available regarding the use of citalopram or escitalopram for OCD. Refer to Chapter 3 for more information regarding SSRl antidepressants. 

Beta agonists (terbutaline, albuterol) Theophylline Antidepressants Bupropion Citalopram Escitalopram Duloxetine Fluoxetine Fluvoxamine... 

Due to the frequent unwanted effects and, in case of tranylcypromine, the numerous and dangerous interactions MAO-inhibitors are more and more replaced by the much less problematic SSRIs. Compounds belonging to this group are citalopram, escitalopram, fluoxetine, paroxetine and sertraline. They are used clinically in the therapy of depression, bulimia and obsessive-compulsive disorders. All SSRIs show a slow onset of action (1-2 weeks). They may induce insomnia and weight loss. The antidepressant ven-lafaxine inhibits both, serotonin and noradrenaline re-uptake and might therefore additionally induce hypertension. 

Escitalopram is manufactured by Forest under the brand name Lexapro, and comes in a 10- or 20-mg tablet. Escitalopram is an antidepressant, but can also be prescribed for generalized anxiety disorder. 

Generahzed anxiety disorder can be treated with benzodiazepines, buspirone, and certain antidepressants (e.g., venlafaxine, paroxetine, escitalopram). These agents are compared in Table 3-3. 

The selective serotonin reuptake inhibitors (SSRIs) represent a chemically diverse class of agents that have as their primary action the inhibition of the serotonin transporter (SERT) (Figure 30-3). Fluoxetine was introduced in the United States in 1988 and quickly became one of the most commonly prescribed medications in medical practice. The development of fluoxetine emerged out of the search for chemicals that had high affinity for monoamine receptors but lacked the affinity for histamine, acetylcholine, and adrenoceptors that is seen with the tricyclic antidepressants (TCAs). There are currently six available SSRIs, and they are the most common antidepressants in clinical use. In addition to their use in major depression, SSRIs have indications in GAD, PTSD, OCD, panic disorder, PMDD, and bulimia. Fluoxetine, sertraline, and citalopram exist as isomers and are formulated in the racemic forms, whereas paroxetine and fluvoxamine are not optically active. Escitalopram is the S enantiomer of citalopram. As with all antidepressants,... 

Several LC-MS and LC-MS/MS methods were developed in plasma for only one antidepressant and, sometimes, its major metabolite(s) to perform pharmacokinetic, bioavailability, or bioequivalence studies. Analytical methods developed for these purposes require very low LLOQ values and, usually, narrow linear ranges covering the low range of the therapeutic concentrations are validated. In this context, several methodologies were described for the determination of fluoxetine [94, 95, 98-100], paroxetine [44, 71, 85, 101, 102], venlafaxine [48, 61, 64, 86, 103,104], sertraline [62, 68, 83], citalopram [46, 89] and escitalopram [105], mianserine [106, 107], mirtazapine [42], trazodone [84], nefazodone [51, 81], duloxetine [47, 50, 73], and bupropion [43], Deuterated analogues of the analyte of interest or of other drugs were employed by few authors as IS [43, 61, 73, 81, 85, 99] however, in most of these methods, another antidepressant or other therapeutic drug was used for this purpose. 

An example of improved efficacy of an enantiomerically pure version of a drug over the racemic version is provided by citalopram. The racemic version, known as Celexa, is marketed as an antidepressant. Studies on the resolved enantiomers have shown that the S-enantiomer is the active one and that it has a more rapid onset of action and a more favorable benefit-to-risk ratio than the racemate. As a result, (S)-citalo-pram (escitalopram or Lexapro) is now being marketed. Not only is this a better and safer drug, but the pharmaceutical company that developed citalopram was able to extend its markel exclusivity for an additional 3 years. 

These selective serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and, most recently, escitalopram (Lexapro see the appendix). These drugs block the removal of the neurotransmitter serotonin from the synaptic cleft. A number of other antidepressants are potent nonselective serotonin reuptake inhibitors (NSRIs). These include the atypical venlafaxine (Effexor) and the tricyclic clomipramine (Anafra-nil). Nefazodone (Serzone) has been withdrawn from the market due to liver damage. 

However, the agency s conclusions were based on a limited number of new antidepressants, including bupropion, citalopram, fluoxetine, flu-voxamine, mirtazapine, nefazodone, paroxetine, sertraline, escitalopram, and venlafaxine, according to an FDA Talk Paper (2004a). These were the drugs most often cited by the public at the two FDA hearings. 

The selective serotonin re-uptake inhibitors (SSRIs) that are currently available are fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram. They are widely marketed and are in many countries a major alternative to tricyclic antidepressants in the treatment of depression. The SSRIs are structurally diverse, but they are all inhibitors of serotonin uptake, with much less effect on noradrenaline. They have slight or no inhibitory effect on histaminergic, adrenergic, serotonergic, dopaminergic, and cholinergic receptors (1). 

FLUVOXAMINE BRONCHODILATORS- THEOPHYLLINE Possible t plasma concentrations of theophylline Fluvoxamine is potent inhibitor of CYP1A2, and fluoxetine is less potent as an inhibitor. Paroxetine, sertraline, escitalopram and citalopram are not currently known to cause any inhibition Consider an alternative antidepressant... 

ANTIDEPRESSANTS-duloxetine, modobemide, SSRIs - escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, TCAs - amitriptyline, clomipramine, desipramine, doxepin, imipramine... 

Venlafaxine and escitalopram may be the best tolerated when switching or augmenting with a serotonin reuptake inhibitor, as neither is a potent CYP450 2D6 inhibitor (use combinations of antidepressants with caution as this may activate bipolar disorder and suicidal ideation)... 

Citalopram is a racemic mixture of S and R isomers.The antidepressant activity of citalopram appears to reside in the S-isomer. Escitalopram the pure S-isomer, may offer clinical benefits over existing preparations. 

Note The most frequently prescribed antidepressant drugs are sertraline (Zoloft), escitalopram (Lexapro). and venlafaxine (Effexo. ... 

The antidepressants can be dosed once a day (see Table 69-7). The initial dose of venlafaxine extended-release is 75 mg once a day 37.5 mg can be used in some patients. The dose can be increased every 4 days up to a maximum of 225 mg once daily, although a dose-response relationship has not been established. Paroxetine is administered in a single daily dose (with or without food) of 20 mg. Doses greater than 20 mg/day have not been found to be more effective, but it can be increased by 10 mg/day every week. Escitalopram dosing begins with 10 mg daily. ... 

Reuptake inhibitors, which include the tricyclic and tetracyclic antidepressants (TCAs and TeCAs),the SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), the serotonin and norepinephrine reuptake inhibitors (SNRIs duloxetine, milnacipran, and venlafaxine), and the norepinephrine and dopamine reuptake inhibitor (bupropion). 

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