Antidepressants for depression

Mottram P, Wilson K, Strobl J. Antidepressants for depressed elderly. Cochrane Database Syst Rev 2006 (1) CD003491. 

Equally effective as other tricyclic antidepressants for depression fewer anticholinergic effects than tertiary amines, less orthostasis, and mild stimulatory property... 

Based on our results, we conclude that SRIs are more effective than placebo or other standard antidepressants in the treatment of OCD, although equieffective to standard antidepressants for depression. Our review distinguished the antiobsessive properties from the antidepressant properties of these agents. 

Cipriani A et al Metareview on short-term effectiveness and safety of antidepressants for depression An evidence-based approach to inform clinical practice. Can J Psychiatry 2007 52(9) 553. [PMID 17953159]... 

Geddes JR et al SSRIs versus other antidepressants for depressive disorder. Cochrane Database Syst Rev 2000 (2) CD001851. 

Aggressively treat concomitant symptoms with augmentation (e.g., atypical antipsychotics for agitation, antidepressants for depression)... 

Alprazoiam (Xanax) Benzodiazepine with anxiolytic activity. Mechanism of antidepressant effects unknown. Adjunct to tricyclic antidepressants for depression and panic attacks. No anticholinergic effeas. Does cause sedation and lethargy. ... 

Geddes, J.R., Freemantle, N., Mason, J., Eccles, M.P., and Boynton, 1. 2000. SSRls versus other antidepressants for depressive disorder. Cochrane Database Syst. Rev. CD001851. 

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... 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

Antidepressant Drugs. Figure 1 Effects of stress as a model for depression and the reversal by the use of antidepressants. Multiple intracellular targets might be involved in the regulation of plasticity and resilience by antidepressants, which block extracellular transporters. Adapted from [1],... 

The authors concluded that antidepressants exert a modest beneficial effect for patients with combined depressive disorder and substance use disorder. They also emphasized that antidepressants are not a stand-alone treatment for depressed alcoholic patients and that concurrent therapy directly targeting the substance use disorder is also indicated. 

Stimulants induce both tolerance and sensitization to their behavioral effects. Tolerance develops to the anorectic and euphoric effects of stimulants (Schuster 1981) however, chronic intermittent use of low doses of stimulants delays the development of tolerance. With the doses commonly used in clinical practice, patients treated for narcolepsy or for depressive or apathetic states find that the stimulant properties usually persist without development of tolerance however, the persistence of antidepressant effects remains a matter of controversy. Sensitization has been linked to the development of amphetamine-induced psychosis (Yui et al. 1999). Sensitization to the induction of psychosis is suggested because psychosis is induced by progressively lower doses and shorter periods of consumption of amphetamine following repeated use over time (Sato 1986). Sensitization for amphetamine-induced psychosis may persist despite long periods of abstinence. 

The use of animal models for depression has two main objectives. One is to provide a behavioural model that can be used to screen potential antidepressant treatments. For this, the behaviour does not have to be an animal analogue of depression all that is needed is for it to be consistently prevented by established antidepressant agents (i.e. no false negatives) but not by drugs which have no antidepressant effect in humans (i.e. no false positives). 

A logical conclusion from this work was that depression is caused by hyperresponsive )S-adrenoceptors. At first, this might seem to undermine Schildkraut s suggestion that depression is caused by a deficit in noradrenergic transmission. However, proliferation of receptors is the normal response to a deficit in transmitter release and so the opposite change, dowmegulation of jS-adrenoceptors by antidepressants, would follow an increase in the concentration of synaptic noradrenaline. This would be consistent with both their proposed mechanism of action and the monoamine theory for depression. 

Anisman, H and Zacharko, RM (1991) Multiple neurochemical and behavioural consequences of stressors implications for depression. In Psychopharmacology of Anxiolytics and Antidepressants (Ed. File, SE), Pergamon Press, New York, pp. 57-82. 

Differentiating between depression and dementia can be difficult, so symptoms of depression should be documented for several weeks prior to initiating therapy for the treatment of depression with AD. Citalopram and sertraline are recommended as first-line agents because of their efficacy in placebo-controlled trials.49 Indications for the use of antidepressants include depression characterized by poor appetite, insomnia, hopelessness, anhedonia, withdrawal, suicidal thoughts, and agitation. 

Trazodone routinely causes sedation, which is why it is used far more often as an adjunct with other antidepressants for sleep than as a primary agent for the treatment of depression. Priapism is a rare but serious adverse effect in males who take trazodone. In addition, orthostatic hypotension and dizziness are more common with trazodone than with nefazodone because the latter agent has a weaker effect at a-adrenergic receptors and also has a balancing of adrenergic effects owing... 

The primary treatment for depressive episodes in bipolar disorder is mood-stabilizing agents, often combined with antidepressant drugs. 

Gijsman HJ, Geddes JR, Rendell JM, et al. Antidepressants for bipolar depression a systematic review of randomized, controlled trials. Am J Psychiatry 2004 161 1537-1547. 

Panic disorder patients are more likely to experience stimulantlike side effects than patients with major depression and should be initiated on lower doses of antidepressant than those that are used for depression or other anxiety disorders. 

Antidepressants have a delayed onset of antipanic effect, typically 4 weeks, with optimal response at 6 to 12 weeks. Reduction of anticipatory anxiety and phobic avoidance generally follows improvement in panic symptoms. PD patients are more likely to experience stimulant-like side effects than patients with depression, and they should be initiated on lower doses (Table 37-6) of antidepressant than those that are used for depression or other... 

If sedatives, barbiturates, antipsychotic drugs, stimulants, opiates and thyroid medications all outperform inert placebos in the treatment of depression, does this mean that any active drug can function as an antidepressant Apparently not. In September 1998 the pharmaceutical company Merck announced the discovery of a novel antidepressant with a completely different mode of action than other medications for depression. This new drug, which they later marketed under the trade name Emend for the prevention of nausea and vomiting due to chemotherapy, seemed to show considerable promise as an antidepressant in... 

At first, Sapirstein and I found the equivalence between antidepressants and other drugs puzzling, to say the least. Why should drugs that are not antidepressants be as effective as antidepressants in treating depression To answer this question, we asked another. What do all these diverse drugs have in common that they do not share with inert placebos What do SSRIs have in common with the older tricyclic antidepressants, with other less common antidepressants, and even with tranquillizers, depressants and thyroid medication The only common factor that we were able to note was that they all produce easily noticeable side effects - the one thing that was lacking in Merck s new treatment for depression. Placebos can also produce side effects, but they do so to a much lesser extent than active medication. Clinical trials show that whereas the therapeutic benefits of antidepressants are relatively small when compared to placebos, the difference in side effects is substantial.7... 

Most clinical trials, including the ones my colleagues and I analysed, are conducted on volunteers, many of whom are recruited for the trial by advertisements. Perhaps these depressed people are not as responsive to antidepressants as the patients seen in clinical practice. The STAR D trial that I described earlier was designed specifically to evaluate the effect of antidepressants on the kinds of patients who are typically seen in clinical practice. None of the patients in this trial were recruited by advertising. Instead, they were all patients who sought treatment for depression in family practice or psychiatric out-patient treatment facilities. Also, the usual exclusion criteria were relaxed, so that a broader range of patients was evaluated. The trial did exclude patients who had already tried antidepressants but had not responded to them, although this exclusion should result in better response rates, not worse ones. 

When the chemical-imbalance theory was introduced more than 40 years ago, the main evidence in favour of it was the contention that antidepressants, which were thought to increase the availability of serotonin and/or other neurotransmitters in the brain, seemed to be effective in the treatment of depression. As Alec Coppen wrote in 1967, one of the most cogent reasons for believing that there is a biochemical basis for depression or mania is the astonishing success of physical methods of treatment of these conditions. 26 The situation has not changed very much since then. People still cite the supposed effectiveness of antidepressants as fundamental support for the chemical-imbalance hypothesis. This theory, they say, is supported by the indisputable therapeutic efficacy of these drugs .27... 

Although placebo effects are generally referred to as nonspecific, there is also a sense in which they are very specific. The effect of the placebo is specific to the beliefs that people have about the substance they are ingesting. Placebo morphine, for example, reduces pain, whereas placebo antidepressants reduce depression. Even the side effects that people report when given a placebo tend to be the same side effects that are produced by the real drug.12 In other words, the effect of a placebo is specific to the effect that the person expects it to have. When given placebo stimulants like decaffeinated coffee (presented as regular coffee), people feel more alert, and their heart rate and... 

Psychotherapy looks even better when its long-term effectiveness is assessed.17 Formerly depressed patients are far more likely to relapse and become depressed again after treatment with antidepressants than they are after psychotherapy. As a result, psychotherapy is significantly more effective than medication when measured some time after treatment has ended, and the more time that has passed since the end of treatment, the larger the difference between drugs and psychotherapy. This long-term advantage of psychotherapy over medication is independent of the severity of the depression. Psychotherapy outperforms antidepressants for severely depressed patients as much as it does for those who are mildly or moderately depressed.18... 

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