Antidepressants specific agents

In summary, although it is difficult to recommend a specific agent for long-term maintenance, because of compliance, convenience, and safety reasons, the newer antidepressants (e.g., SSRls, venlafaxine] appear to be agents of first choice. Because the long-term database for these agents is less extensive than that for TCAs, further studies are indicated. 

The monoamine hypothesis, like the neurotrophic hypothesis, is at best incomplete. Many studies have not found an alteration in function or levels of monoamines in depressed patients. In addition, some candidate antidepressant agents under study do not act directly on the monoamine system. These include glutamate antagonists, melatonin agonists, and glucocorticoid-specific agents. Thus, monoamine function appears to be an important but not exclusive factor in the pathophysiology of depression. 

The use of antidepressants outside the treatment of MDD tends to require specific agents. For example, the TCAs and SNRIs appear to be useful in the treatment of pain conditions, but other antidepressant classes appear to be far less effective. SSRIs and the highly serotonergic TCA, clomipramine, are effective in the treatment of OCD, but noradrenergic antidepressants have not proved to be as helpful for this condition. Bupropion and nortriptyline have usefulness in the treatment of smoking cessation, but SSRIs have not been proven useful. Thus, outside the treatment of depression, the choice of antidepressant is primarily dependent on the known benefit of a particular antidepressant or class for a particular indication. 

Problems and side effects associated with buspirone include dizziness, headache, nausea, and restlessness. Antidepressants such as paroxetine and venlafaxine also produce a number of side effects (described in Chapter 7) depending on the specific agent. Nonetheless, these newer, nonbenzodiazepine... 

For pharmaceutical purposes 2000-3000 tonnes of amino acids are required annually worldwide. More than half of this amount ends up in infusion solutions for artificial nutrition. Many amino acid derivatives are pharmacologically important acetylcysteine is mucolytic, (L)-DOPA an active agent to combat Parkinson s disease, and Oxitriptan ((S)-5-hydroxytryptophan) is an antidepressant. Specifically substituted, (D)-configured, a- and /3-amino acids find widespread application as building blocks for drug synthesis. 

Future Outlook for Antidepressants. Third-generation antidepressants are expected to combine superior efficacy and improved safety, but are unlikely to reduce the onset of therapeutic action in depressed patients (179). Many dmgs in clinical development as antidepressive agents focus on estabhshed properties such as inhibition of serotonin, dopamine, and/or noradrenaline reuptake, agonistic or antagonistic action at various serotonin receptor subtypes, presynaptic tt2-adrenoceptor antagonism, or specific monoamine—oxidase type A inhibition. Examples include buspirone (3) (only... 

Most of the serotonin in the brain is in the brainstem, specifically in the raphe nuclei considerable amounts also are present in areas of the hypothalamus, the limbic system, and the pituitary gland. Current evidence indicates that serotonin is involved in the regulation of several aspects of behavior, including sleep, pain perception, depression, sexual activity, and aggressiveness. Some of the most important antidepressant agents are believed to prevent the reuptake of serotonin (see Chapter 33). Serotonin also may be involved in temperature regulation and in the hypothalamic control of the release of pituitary hormones. 

This chapter will review available atypical antidepressants and will specifically discuss their uses in children and adolescents. At this time, it is important to note that none of the agents discussed in the chapter have an FDA indication for use in children and adolescents however, the use of these agents in children and adolescents is increasing, and knowledge of these agents is critical for both research and clinical practice. 

No specific antiaggressive agent exists for children. Flowever, antipsychotics, anticonvulsants, mood stabilizers, antidepressants, sedative-anxiolytics, and beta-blockers are all used to target aggression. Unfortunately, few controlled studies exist that assess these agents. 

Some patients with bipolar disorder will need antidepressants. Although the switch rate into mania or induction of rapid cychng by antidepressants is controversial, these agents do appear to present a risk for some patients, often with devastating consequences. Therefore, when a patient with bipolar disorder is prescribed an antidepressant, it should only be in combination with a medication that has established antimanic properties. Controlled comparative data on the use of specific antidepressant drugs in the treatment of bipolar depression are sparse. Current treatment guidelines extrapolate from these few studies and rely heavily on anecdotal chnical experience. Overah, tricyclic antidepressants should be avoided when other viable treatment options exist. Electroconvulsive therapy should be considered in severe cases. 

Specific factors to consider are both psychiatric and physical contraindications. For example, bupropion is contraindicated in a depressed patient with a history of seizures due to the increased risk of recurrence while on this agent. Conversely, it may be an appropriate choice for a bipolar disorder with intermittent depressive episodes that is otherwise under good control with standard mood stabilizers. This consideration is based on the limited data suggesting that bupropion is less likely to induce a manic switch in comparison with standard heterocyclic antidepressants. Another example is the avoidance of benzodiazepines for the treatment of panic disorder in a patient with a history of alcohol or sedative-hypnotic abuse due to the increased risk of misuse or dependency. In this situation, a selective serotonin reuptake inhibitor (SSRI) may be more appropriate. 

During all phases of treatment, education, supportive therapy, and, at times, more specific types of psychotherapy are essential for a satisfactory outcome. For example, interpersonal therapy can complement adequate maintenance antidepressant treatment, possibly diminishing the frequency of episodes (see the section Role of Psychosocial Therapies in Chapter 7), and cognitive-behavioral techniques in combination with antiobsessive agents (e.g., clomipramine) can improve the quality of life for patients with obsessive-compulsive disorder, minimizing time spent on disabling rituals (see the section Obsessive-Compulsive Disorder in Chapter 13). 

Because many have suggested that the beneficial effect of antidepressants is based on their ability to block the uptake of NE and 5-HT, pharmaceutical companies screen potential antidepressants for their ability to block neurotransmitter uptake. Partially as a result of this paradigm (i.e., reuptake blockade), the industry has developed agents that can specifically block NE uptake, 5-HT uptake, or both. More recently, drugs that also affect specific receptors or receptor subtypes have been... 

Nefazodone has some unusual pharmacological properties, not only inhibiting serotonin uptake, but also blocking the 5-HT 2a receptor. It may be that the antidepressant effect of serotonin agents is due to mediation of 5-HT transmission in the absence (or even the blockade) of 5-HT2a transmission. As a result of these actions, nefazodone is even more specific in terms of affecting a subtype of serotonin receptor than are the SSRIs or venlafaxine. 

An important aspect of antidepressant pharmacotherapy is selection based on the adverse effect profile of a specific medication, because most antidepressants are comparable in terms of efficacy. One of the major accomplishments of modern antidepressant development has been to improve the adverse effect profile of newer agents in comparison with TCAs and MAOIs without compromising efficacy (1). That has been accomplished by developing chemicals that retain the ability to affect sites of action that appear to be capable of mediating antidepressant efficacy (e.g., the serotonin uptake pump), but avoid effects on unnecessary sites of action (e.g., ACh receptor, fast sodium channels). This approach has led to both better tolerated and safer medications. Table 7-23 lists the common potential adverse affects of a number of antidepressants, as well as their relative severity. 

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