Venlafaxine imipramine

Note In a survey of 13 studies, switching from an SSRI to either another SSRI or to imipramine, venlafaxine, mirtazepine or buproprion resulted in a response rate of 30-90%. 

SNRIs are chemically unrelated to each other. Venlafaxine was discovered in the process of evaluating chemicals that inhibit binding of imipramine. Venlafaxine s in vivo effects are similar to those of imipramine but with a more favorable adverse-effect profile. All SNRIs bind the serotonin (SERT) and norepinephrine (NET) transporters, as do the TCAs. However, unlike the TCAs, the SNRIs do not have much affinity for other receptors. Venlafaxine and desvenlafaxine are bicyclic compounds, whereas duloxetine is a three-ring structure unrelated to the TCAs. Milnacipran contains a cyclopropane ring and is provided as a racemic mixture. 

SSRI (most studied with paroxetine), imipramine, venlafaxine or Buspirone, hydroxyzine... 

The manufacturer recommends caution when atomoxetine is given concurrently with other drugs that affect noradrenaline, because of the potential for additive or synergistic pharmacological effects. Examples they name are antidepressants such as imipramine, venlafaxine and mirtaza-pine, and the decongestants pseudoephedrine or phenylephrine. Until more is known, this would seem a sensible precaution. 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Antidepressants Desipramine, imipramine, sertraline, fluoxetine, paroxetine, venlafaxine, bupropion, nefazodone, mirtazapine, gepirone, amineptine Mixed findings suggest that better designed studies may find a niche for some of these drugs. Amineptine was effective for withdrawal symptoms. 

Decision analytic models have been constmcted to compare the costs of TCAs with those of SSRIs and other compounds. These comparisons have included imipramine or amitriptyline versus paroxetine or sertraline (Stewart, 1994) imipramine versus paroxetine Qonsson and Bebbington, 1994 McFarland, 1994 Lapierre et al, 1995) fluoxetine versus amitriptyline, clomipramine, doxepin and imipramine (Le Pen et al, 1994) venlafaxine versus amitriptyline, desipramine. 

Generalized anxiety Duloxetine Escitalopram Paroxetine Venlafaxine XR Benzodiazepines Buspirone Imipramine Sertraline Hydroxyzine Pregabalin... 

Panic disorder SSRIs Venlafaxine XR Alprazolam Clomipramine Clonazepam Imipramine Phenelzine... 

Venlafaxine extended release, duloxetine, paroxetine, and escitalopram are FDA approved for treatment of GAD. Sertraline is also effective. Acute response and remission rates are approximately 65% and 30%, respectively. Imipramine may be used when patients fail to respond to selective serotonin reuptake inhibitors (SSRIs). In one trial, diazepam, trazodone, and imipramine had greater anxiolytic activity than placebo. 

Amitriptyline and imipramine, and the MAOI phenelzine, can be considered second- or third-line drugs for PTSD after SSRIs have failed. Mirtaza-pine and venlafaxine may also be effective. 

The most effective treatment for cataplexy is the tricyclic antidepressants, fluoxetine, or venlafaxine. Imipramine, protriptyline, clomipramine, fluoxetine, and nortriptyline are effective in about 80% of patients. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

Solid phase extraction (SPE) has been used to efficiently extract several types of antidepressants, which can then be conveniently analyzed on GC-NPD. One assay extracted and analyzed viloxazine, venlafaxine, imipramine, desipramine, sertraline, and amoxapine from whole blood in one procedure (Martinez et al., 2002). The same laboratory analyzed fluoxetine, amitriptyline, nortriptyline, trimipramine, maprotiUne, clomipramine, and trazodone in whole blood in one assay (Martinez et al., 2003). SPE has also been used for the simultaneous analysis of TCAs and their metabolites by de la Torre et al. (1998). 

Lorazepam is a short-acting benzodiazepine indicated for use in relieving anxiety and insomnia. Lorazepam may also be administered perioperatively to alleviate pain and in status epilepticus. Imipramine is a tricyclic antidepressant, paroxetine is a selective serotonin re-uptake inhibitor, venlafaxine is a serotonin and adrenaline re-uptake inhibitor and moclobemide is a reversible monoamine oxidase inhibitor. Imipramine, paroxetine, venlafaxine and moclobemide are all classified as antidepressants. 

Amitriptyline, clomipramine, imipramine, desipramine, nortriptyline, trimipramine, AT-desmethylclomipramine, fluvoxamine, norfluoxetine, paroxetine, venlafaxine, sertraline Neuroleptics... 

FIGURE 2.6 Serotonergic synapse. Serotonin binds to at least seven different receptors. The most relevant are the 5-HTi receptors (1), 5-HT2 receptors (2), and 5-HT3 receptors (3). Antagonists of the 5-HT2 receptor include nefazodone and the majority of atypical antipsychotic drugs. The serotonin transporter (4) pumps serotonin back into the serotonergic neuron, which can be blocked by drugs such as venlafaxine, clomipramine, imipramine, and amitriptyline. 

Ball, S.E., Ahem, D., Scatina, J., and Kao, J. (1997) Venlafaxine in vitro inhibition of CYP2D6 dependent imipramine and desipra-mine metabolism comparative studies with selected SSRIs, and... 

ADHD, attention-deficit hyperactivity disorder BP, blood pressure CLO, clomipramine FLX, fluoxetine IMP, imipramine N, total number of subjects in study ( ), number of preschool-age subjects in study P, pulse rate PDD-NOS, pervasive developmental disorder, not otherwise specified SE, side effect VNF, venlafaxine. DSM-III-R or DSM-IV criteria used not specified by authors. 

Venlafaxine, paroxetine, sertraline, imipramine, and trazodone have all proven effective in relieving symptoms of GAD. Venlafaxine, a combined serotonin and norepinephrine reuptake blocker, may be an exceptionally good choice for people who have other psychiatric illnesses in addition to GAD, or when it is not clear whether the patient has GAD or a depressive illness, or both. Although, to date, only certain SSRIs have been... 

Several preliminary lines of research have started to suggest that antidepressants, once considered ineffective in generalized anxiety disorder, may be very efficacious [Gorman and Kent 1999]. In particular, venlafaxine has been effective in treating generalized anxiety disorder in both open-label and double-blind trials, and imipramine and paroxetine were as effective as a benzodiazepine in the long-term treatment of generalized anxiety disorder. 

The advantage of venlafaxine in terms of more rapid onset of action is apparently only seen when the drug is escalated rapidly to the high dose. In a recent study comparing venlafaxine with imipramine in inpatients with severe depression, a significant difference was observed between the two active treatments by the second week [Benkert et al. 1996. ... 

Another approach to correct neurotransmission is to inhibit the reuptake of the neurotransmitters into their presvnaptic endings. If the presynaptic reuptake mechanism of a neurotransmitter is blocked then more of the neurotransmitter will stay in the synaptic cleft and be functionally available. Many antidepressant drugs, called reuptake inhibitors , are thought to act via this mechanism. If selective for serotonin they are called selective serotonin reuptake inhibitors (SSRIs, Chapter 1), but if selective for both serotonin and noradrenaline they are called serotonin noradrenaline reuptake inhibitors (SNRIs). Most older antidepressants, such as the tricyclic compounds amitriptyline, imipramine and clomipramine, have little specificity for any of the neurotransmitters fluoxetine, paroxetine, citalopram and a few others are specific for serotonin venlafaxine is a representative of the SNRIs. A more recent mixed-uptake inhibitor is mirtazepine, and some similar compounds are about to be launched. 

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

Those who fail to respond to an SSRI may respond to a TCA, and vice versa. Thus, these two broad-spectrum classes can be used in a sequential strategy to adequately treat the majority of cases. However, many physicians try another newer antidepressant (e.g, venlafaxine, bupropion, nefazodone) in such patients because of the safety and tolerability problems associated with TCAs. Of note, the tolerability profile of secondary amine TCAs such as desipramine is as favorable as any of the newer antidepressants and probably better than nefazodone. Nevertheless, the secondary amine TCAs have a therapeutic index as narrow as tertiary amine TCAs (e.g., amitriptyline, imipramine) in terms of lethality in overdoses resulting from cardiotoxicity. 

The one study done to date with venlafaxine used a double-blind continuation design rather than a crossover design used with the SSRIs ( Table 7-21). Responders in the double-blind, placebo- and active-controlled acute efficacy phase could elect to remain on double-blind treatment for a 1-year follow-up phase ( 271). The treatment arms in these studies included venlafaxine, trazodone, imipramine, and placebo. At the end of 1 year, 18% of patients on venlafaxine had relapsed versus 32% on placebo. The difference between the venlafaxine and the placebo groups was smaller than that seen between the SSRIs and their respective placebo groups (Table 7-20), consistent with the difference in the design of these studies. 

As with venlafaxine, a double-blind continuation study has been done with nefazodone (see Jable 7-21). Patients who responded to nefazodone, imipramine, or placebo in the acute phase were offered the option of remaining on double-blind treatment for 1 year ( 272). Those patients who chose to participate were then followed up monthly to assess whether efficacy persisted. The relapse rate was 22% on placebo versus 10% on nefazodone and 7% on imipramine. The absolute difference in relapse rates between nefazodone and placebo was similar to that of venlafaxine versus placebo (i.e., 12% to 14%). Thus, maintenance treatment with nefazodone, as with venlafaxine and the SSRIs, reduced the risk of relapse when compared with placebo even when the comparison group had initially responded to placebo and remained on placebo for the maintenance period. 

Grunder G, Wetzel H, Schloer R, et al. Subchronic antidepressant treatment with venlafaxine or imipramine and effects on blood pressure assessment by automatic 24 hour monitoring. Pharmacopsychiatry 1993 26 155. 

The other tertiary TCA that has dual serotonergic-noradrenergic effects, amitriptyline, like imipramine, appears to be consistently effective in anxiety disorders. Newer antidepressants such as mirtazapine, nefazodone, paroxetine, and venlafaxine may also benefit patients with anxiety disorder ( 60, 61, 62 and 63). 

OFFICIAL NAMES Amitriptyline (Elavil), amoxapine (Asendin), bupropion (Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), fluoxetine (Prozac), imipramine (Norfranil, Tofranil), isocarboxazid (Marplan), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Aventyl, Pamelor), paroxetine (Paxil), phenelzine (Nardil), protriptyline (Vivactil), sertraline (Zoloft), thioridazine (Mellaril), tranylcypromine (Parnate), trazodone (Desyrel), trimipramine (Sur-montil), venlafaxine (Effexor) the herb St. John s wort (Hypericum perforatum) is sold over-the-counter without prescription STREET NAMES Happy pills... 

Cyt 2D6 metabolizes haloperidol, risperidone, thioridazine, sertindole, olanzapine and clozapine common substrates - fluoxetine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, propranolol, metoprolol, timolol, codeine, encainide, flecanide. Common inhibitors - paroxetine, sertraline, fluoxetine. 

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