Antidepressant alternatives

Because 25% of patients will stop SSRIs due to side effects and an additional 30% to 40% will fail to achieve a therapeutic response, other antidepressant alternatives are of great importance. Venlafaxine is a dual-action antidepressant that enhances serotonin activity at low doses and norepinephrine at higher doses. Preliminary evidence suggests that these multiple actions on neurotransmitters may confer therapeutic superiority over SSRIs for the management of severe or melancholic depression, but the risk of HTN with high-dose venlafaxine should not be overlooked. 

Reversible Inhibitors of Monoamine Oxidase. Selective MAO-A inhibitors, which aie leveisible (so-called RIMAs), have also been developed, theiefoie substantially leduciag the potential foi food and dmg iateiactions. Indeed, the tyiamine-potentiating effects of these dmgs is much reduced compared with the irreversible MAO inhibitors. The RIMAs represent effective and safer alternatives to the older MAO inhibitors. The only marketed RIMAs ate toloxatone [29218-27-7] and moclobemide (55). The latter is used widely as an effective, weU-tolerated antidepressant. 

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

Two closely related indoles fused to an additional saturated ring have been described as CNS agents. The first of these is obtained in straightforward manner by Fischer indole condensation of functionalized cyclohexanone 0 with phenyl hydrazine (19). The product, cyclindole (21) shows antidepressant activity. The fluorinated analogue flucindole (26) can be prepared by the same scheme. An alternate route starting from a somewhat more readily available intermediate involves as the first step Fischer condensation of substituted phenyl hydrazine with 4-hydroxycyclohexanone (23). The resulting alcohol (24) is then converted to its tosylate (25). Displacement by means of dimethyl amine leads to the antipsychotic agent flucindole (26). ... 

Various forms of psychotherapy are regarded as effective interventions in mild to moderate depression, but studies comparing the economics of psychotherapy and pharmacotherapy are few (Rosenbaum and Hylan, 1999). One study found that the total health-care costs for patients who received psychotherapy were no different from those for patients who received an antidepressant. However, no efficacy measure was used (Edgell and Hylan, 1997). A randomized, prospective study which evaluated the treatment of depression with nortriptyline, interpersonal therapy or treatment as usual, with outcomes expressed in quality-adjusted life years, found that nortriptyline but not interpersonal therapy was a cost-effective alternative to treatment as usual (Lave et al, 1998). 

Geddes JR, Freemantle N, Mason J, Eccles MP, Boynton J (1999). SSRIs versus alternative antidepressants in depressive disorder (Cochrane Review). In Cochrane Library, Issue 4. Oxford Update Software. 

This interaction is the same as the one when clonidine is combined with TCAs however, mirtazapine is a more potent a2-receptor blocker than the TCAs avoid this interaction and choose an alternative antidepressant without a2-blocking effects. 

Antidepressant medications appear to be useful for certain children and adolescents, particularly those who have severe or psychotic depression, fail psychotherapeutic measures, or experience chronic or recurrent depression. SSRIs generally are considered the initial antidepressants of choice, although comorbid conditions may favor alternative agents. Clinicians should be aware of the possibility of behavioral activation with the SSRIs, including such symptoms as impulsivity, silliness, daring conduct, and agitation.44 Desipramine should be used with caution in this population because of several reports of sudden death, and a baseline and follow-up electrocardiogram (ECG) may be warranted when this medication is used to treat pediatric patients.9... 

Overall, non-hormonal therapies are less effective in treating vasomotor symptoms than HRT but do offer an important option for women experiencing menopausal symptoms who cannot or are unwilling to take HRT. The antidepressants gabapentin and clonidine have the best evidence for efficacy of all the non-hormonal options and should be considered first as an alternative to HRT. The most important considerations in choosing an alternative therapy are the patient s comorbidities and the efficacy and safety of the medication. 

Much of what 1 write in this book will seem controversial, but it is all thoroughly grounded on scientific evidence - evidence that I describe in detail in this book. Furthermore, as controversial as my conclusions seem, there has been a growing acceptance of them. NICE has acknowledged the failure of antidepressant treatment to provide clinically meaningful benefits to most depressed patients the UK government has instituted plans for providing alternative treatments and neuroscientists have noted the inability of the chemical-imbalance theory to explain depression.6 We seem to be on the cusp of a revolution in the way we understand and treat depression. 

Of all the alternatives to antidepressant medication, psychotherapy is the most thoroughly researched. It has been the subject of... 

For society as a whole, knowledge of what the data on antidepressants really say should be a clarion call. Resources need to be made available for the provision of effective alternative treatments, and the social and economic causes of depression need to be addressed and overcome. It is my hope that this book will contribute to a wider recognition of the need for these changes in public policy and attitudes. 

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

Alternatively, the current antidepressant may be augmented (potentiated) by the addition of another agent (e.g., lithium, T3), or an atypical antipsychotic (e.g., risperidone). Risperidone has been shown to be effective in combination with fluvoxamine, paroxetine, or citalopram in treatment-resistant depression. Olanzapine and fluoxetine have been found to be safe and effective in treatment-resistant depression. 

The antidepressants are good alternatives for patients with poor sleep who should not receive benzodiazepines, especially those with depression or a... 

Bupropion is another alternative pharmacological approach to tobacco abstinence. It is an antidepressant drug that blocks reuptake of norepinephrine and dopamine, and also blocks nicotinic receptors in the low to intermediate micromolar range (Fryer and Lukas 1999). Thus, the effects of bupropion on nicotine addiction may be through dual effects on dopaminergic and nicotinic systems. Further, it has been an effective treatment in controlled studies, both alone and in combination with the nicotine patch. Bupropion alone or in combination with a nicotine patch was more effective than placebo or the nicotine patch alone. 

Tricyclic Antidepressants (TCAs). Like iproniazid, the first TCA was also developed in the 1950s for another purpose. Imipramine (Tofranil) is structurally similar to the early antipsychotics and was hoped to provide an alternative to chlor-promazine (Thorazine). It proved to be a poor antipsychotic but was surprisingly found to be an effective antidepressant. The tricyclics are so named because a three-ringed structure forms the hub of the molecule. 

The first decision when beginning acute phase treatment is choosing the primary treatment modality psychotherapy, medication, or both. Several short-term therapies including CBT, IPT, brief psychodynamic therapy, and marital therapy are effective treatments in mild-to-moderate cases of depression without added antidepressant treatment. This is a viable alternative that many patients may prefer. 

When the residual depression is mild to moderate, then the risks of using lithium are probably not warranted. A less aggressive approach using a safer but less proven augmenting medication is best. The alternatives include adding T3, buspirone, pindolol, a second antidepressant, a stimulant, estrogen, or an anticonvulsant. 

T3 is the best studied of these and is a reasonable alternative, but many prefer adding a second antidepressant in order to recapture some of the rich pharmacology of the older antidepressants. Stimulants are highly recommended for medically compromised patients who need a rapid response, and buspirone is probably best... 

Finally, when depressive symptoms persist after treatment with both a mood stabilizer and an antidepressant has been maximized, other treatment alternatives remain. These include the use of electroconvulsive therapy (ECT) or the addition... 

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