Antidepressants clinical efficacy

Trigclic Antidepressants. Imipramine (38) was introduced in the late 1950s as one of the first pharmacotherapies for depression. At that time, chlorproma2ine [50-53-3] was the first effective antipsychotic treatment to be discovered. Researchers looked for similar chemical stmctures and imipramine was found to be effective in the symptomatic treatment of depression. Over the years, other congeners, such as desipramine (39), amitriptyline (40), and dothiepin (41), were synthesized and shown to be clinically efficacious antidepressant dmgs (121). These substances, known under the general mbric of tricycHc antidepressants, share a basic chemical stmcture comprising... 

The second-generation antidepressants, particularly RIMAs and SSRJs, are much less toxic ia overdose than the older TCAs and irreversible MAO inhibitors. However, similar to first-generation antidepressants, the therapeutic effect only becomes manifest after several weeks. Up to one-third of depressed patients are nonresponders. Ideally, an antidepressant would combine a more rapid onset of action with greater clinical efficacy and a higher responder rate, as well as even better tolerability. 

Chinese depressed patients appeared to require lower dosages, with consequently lower plasma concentrations of sertraline compared to Caucasian patients to achieve clinical efficacy (Ng et al, 2006). Again, this finding has supported the fact that Asian patients, especially Chinese, need lower doses of antidepressant drugs than their Western counterparts. 

One aspect of the labeling deserves special mention. The Clinical Efficacy Trials subsection within the Clinical Pharmacology section not only describes the clinical trials providing evidence of citalopram s antidepressant effects, but makes mention of adequate and well controlled clinical studies that fail to do so. I... 

Considerable effort in the field of monoamine reuptake inhibitors is focused on improving antidepressant efficacy since 30-40% of patients do not respond to treatment with currently available agents [6,7], An additional major objective is to enhance the onset of action. Current antidepressants typically require 2-6 weeks of treatment before clinical efficacy is seen [6]. Clinical trials exploring augmentation strategies, in which a DA reuptake inhibitor or a dual NE/DA reuptake inhibitor is combined with an SSRI, have resulted in improved efficacy in depressed patients refractory to SSRI treatment alone [4,5]. The improved results from clinical trials such as these serve to justify the considerable focus on the development of inhibitors that simultaneously block the reuptake of 5-HT, NE and DA. 

Future directions for research on hypericum may continue the work done in clinical efficacy. More specifically, studies may be of interest that examine its effects in treatment of more severe depression and different subtypes of depression. The comparative efficacy of different hypericum preparations could be further investigated, and optimum dosages need to be established (Linde et al. 1996). Further work is needed to compare hypericum s efficacy and side effects with those of the SSRIs or atypical antidepressants, because published studies to date have only compared it with tricyclics. 

The excellent clinical efficacy of the TCAs has been well documented and the pharmacokinetic profiles are favourable. The most serious disadvantage of the TCAs lies in their cardiotoxicity. Thus, with the exception of lofepramine, all the tricyclic antidepressants, including maprotiline, block the fast sodium channels in the heart which can lead to heart block and death. Approximately 15% of all patients with major depression die by suicide and a high proportion of these (up to 25%) do so by taking an overdose of TCAs. Such a dose can be as low as 5-10 times the recommended daily dose. 

In CONCLUSION it appears that the chemically and pharmacologically diverse drugs that act as antidepressants have two properties in common. Firstly, they demonstrate approximately equal clinical efficacy and require several weeks administration to produce an optimal therapeutic effect. Secondly, they all modulate a number of different t)rpes of mainly postsynaptic neurotransmitter receptors in animals and in depressed... 

Fluoxetine, along with sertraline, fluvoxamine, and paroxetine, belongs to the more recently developed group of SSRI. The clinical efficacy of SSRI is considered comparable to that of established antidepressants. Added advantages include absence of cardiotoxicity, fewer autonomic nervous side effects, and relative safety with overdosage. Fluoxetine causes loss of appetite and weight reduction. Its main adverse effects include overarousal, insomnia, tremor, akathisia, anxiety, and disturbances of sexual function. 

Stahl, S. M., Grady, M. M., Moret, C., and Briley, M. (2005). SNRIs Their Pharmacology, Clinical Efficacy, and Tolerability in Comparison with Other Classes of Antidepressants, CNS Spectrums, 10 732-747. 

In summary, these clinical and preclinical findings support the view that mood disorders can be seen as stress system disorders, in which impairment of GR and MR action plays a causal role. The impairments may be genetically determined or acquired through a variety of early stressors, or both. It is possible that antidepressants exert their clinical efficacy through reinstatement of complete corticosteroid receptor function. Of course, other important actions of these drugs also need careful consideration. 

Electroconvulsive therapy (ECT) is an established and effective treatment of depression and some forms of schizophrenia. ECT is the treatment of choice in several types of depression (W. Z. Potter and Rudorfer 1993), especially severe depression (American Psychiatric Association Task Force on Electroconvulsive Therapy 1990 W. Z. Potter et al. 1991). The mechanism by which ECT exerts its antidepressant effect is still unknown. Studies of pharmacologically as well as of electrically induced convulsions suggest that the convulsion is a necessary condition for ECT s therapeutic effects (Cerletti and Bird 1938 Lerer 1987 Lerer et al. 1984). However, there is no satisfactory explanation for the clinical efficacy of convulsions. 

The antidepressant properties of these earlier antidepressants were chance discoveries. Imipramine was first developed as a potential antipsychotic, but when Kuhn (2) tested the clinical efficacy of this agent, he found that it only benefited depressed schizophrenic patients. This observation prompted him to test it in patients who were suffering from melancholia. Iproniazid was developed as an antitubercular drug, but the observation that euphoria was a side effect led George Crane ( 3) to conduct clinical trials, which found it useful in purely depressed patients. A year later, Nathan Kline ( 4), following up on this observation, reported positive results when he administered iproniazid to another depressed group. 

Georgotas A et al Trazodone hydrochloride A wide spectrum antidepressant with a unique pharmacological profile. A review of its neurochemical effects, pharmacology, clinical efficacy, and toxicology. Pharmacotherapy 1982 2(5) 255. [PMID 6763207]... 

There is an impression, in the light of clinical experience, that antidepressants might reduce the clinical efficacy of tamoxifen (116), but more evidence is needed to confirm or reject this view. 

In addition to known antidepressants increasing endogenous opioids, opioid ligands have also been administered to depressed patients to determine if opioid compounds have clinical efficacy to treat depression. The opioid ligand cyclazocine improved symptoms in severely depressed, chronically ill mental patients in an open clinical trial and in clinical trials with patients unresponsive to the tricyclic antidepressant imipramine [16]. Intravenous (5-endorphin infusions improved mood in depressed patients in open case studies [17] and in depressed patients in a double-blind placebo-controlled study [18,19]. However, one study found a trend to improve depression scores in patients after acute and chronic (5-endorphin infusions, but it was not significant [20]. 

Lahti, R. A. Maickel, R. P. 1971, The tricyclic antidepressants - inhibition of norepinephrine uptake as related to potentiation of norepinephrine and clinical efficacy, Biochemical Pharmacology, vol. 20, pp. 482-486. 

IMATINIB 1. ANTIBIOTICS-rifampicin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - dexamethasone 3. ANTIDEPRESSANTS-St John s wort 4. ANTI EPILEPTICS - carbarn azepine, phenobarbital, phenytoin 1 imatinib levels Due to induction of CYP3A4-mediated metabolism of imatinib Monitor for clinical efficacy and adjust dose as required. Avoid co-administration of imatinib and rifampicin... 

PACLITAXEL 1. ANTIBIOTICS-rifampicin 2. ANTIDEPRESSANTS-St John s wort 3. ANTIEPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 plasma concentration of paclitaxel and 1 efficacy of paclitaxel Due to induction of hepatic metabolism of paclitaxel by the CYP isoenzymes Monitor for clinical efficacy and need to T dose if inadequate response is due to interaction... 

VINCA ALKALOIDS - VINBLASTINE, VINCRISTINE 1. ANTIBIOTICS-rifampicin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - dexamethasone 3. ANTIDEPRESSANTS-St John s wort 4. ANTI EPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 of plasma concentrations of vinblastine and vincristine, with risk of inadequate therapeutic response. Reports of 1 AUC by 40% and elimination half life by 35%, and t clearance by 63%, in patients with brain tumours taking vincristine, which could lead to dangerously inadequate therapeutic responses Due to induction of CYP3A4-mediated metabolism Monitor for clinical efficacy, and t dose of vinblastine and vincristine as clinically indicated in the latter case, monitor clinically and radiologically for clinical efficacy in patients with brain tumours and t dose to obtain desired response... 

Khouzam FIR. The antidepressant nefazodone. A review of its pharmacology, clinical efficacy, adverse effects, dosage, and administration. Journal of Psychosocial Nursing and Mental Flealth Services 2000 38 20-25. 

Both depression and anxiety appear to be associated with a dysregulation of serotonergic function at some level, a hypothesis supported by the clinical efficacy of the SSRIs in both disorders. On the other hand, the benzodiazepines have no clinical utility as antidepressants. It has therefore been suggested that, although serotonin has a role in both disorders, different serotonergic pathways and receptor subtypes are responsible for the modulation of anxiety and depression (166, 167). Some of the major 5HT neuronal pathways... 

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