Antidepressant drugs antidepressants side effects

In a manner similar to that observed following treatment with antidepressant drugs, the side effects of dopamine receptor blockade occur rather quickly but the clinical benefits require 2 to 3 weeks, or more, to fully develop. This also implies that compensatory changes in brain function are required for these drugs to produce clinical benefits in psychotic patients. These changes most likely require the activation or inactivation of... 

Dicyclomine (Bentyl), oxybutynin (Ditropan), and tolterodine (Detrol) are nonselective smooth muscle re-laxants that produce relatively little antagonism of muscarinic receptors at therapeutic concentrations. The mechanism of relaxation is not known. Finally, some other classes of drugs can act in part as muscarinic antagonists. For example, the antipsychotics and antidepressants produce antimuscarinic side effects (e.g., dry mouth). 

This group of drugs consists primarily of compounds that block the enzyme monoamine oxidase (MAO). While useful as hypotensive and antidepressant dmgs, their side effects can be serious. We discuss them briefly as enzyme inhibitors in chapter 8. 

The differential includes lethal catatonia, malignant hyperthermia, alcohol withdrawal, infection (encephalitis / menii itis / sepsis) and drug toxicity. SS often presents with low-level discomfort, and may resemble opiate withdrawal, hypomania or antidepressant side effects. 

Chlorpromazine had been shown to produce a tranquil state in animals and since it had a similar effect in humans it became known as a major tranquiliser but the term is rarely used today. Sometimes the drugs used to treat schizophrenia are called anti-psychotics but more commonly neuroleptics. Leptic means to activate (take hold of) and in animals these compounds produce a state of maintained motor tone known as catalepsy. This is an extrapyramidal effect and in schizophrenics the neuroleptics can cause a number of extrapyramidal side-effects (EPSs) including Parkinsonism. The new term neuroleptic is unsatisfactory as a description of clinically useful drugs. It really describes a condition (catalepsy) seen in animals and is more indicative of a compound s ability to produce EPSs than to treat schizophrenia. Antipsychotic is more descriptive but could imply a more general efficacy in psychoses than is the case. It would seem more appropriate to call a drug that is used to treat schizophrenia an antischizophrenic just as we use the terms antidepressant or antiepileptic irrespective of how the drug works. Despite such personal reservations, the term neuroleptic will be used in this text. 

In contrast, iproniazid, introduced in 1951 for treatment of tuberculosis, induced euphoria and was described as a psychic energiser . In fact, these patients, when given iproniazid, could become quite disruptive and this action was regarded as an undesirable side-effect However, its beneficial effects in depression were soon recognised and it was regarded as the first effective antidepressant drug. Studies of peripheral sympathetic neurons, later extended to noradrenergic neurons in the brain, showed that iproniazid irreversibly inhibits the catalytic enzyme, monoamine oxidase (MAO). Because only cytoplasmic monoamines are accessible to MAO, inhibition of this enzyme first increases the concentration of the pool of soluble transmitter but this leads to a secondary increase in the stores of vesicle-bound transmitter i.e. the pool available for impulse-evoked release (Fillenz and Stanford 1981). 

The adverse side-effects of the TCAs, coupled with their toxicity in overdose, provoked a search for compounds which retained their monoamine uptake blocking activity but which lacked the side-effects arising from interactions with Hj, aj-adreno-ceptors and muscarinic receptors. One of the first compounds to emerge from this effort was iprindole, which has an indole nucleus (Fig. 20.3). This turned out to be an interesting compound because it has no apparent effects on monoamine uptake and is not a MAO inhibitor. This, together with its relatively minor antimuscarinic effects, led to it commonly being described as an atypical antidepressant. Mechanisms that could underlie its therapeutic actions have still not been identified but, in any case, this drug has now been withdrawn in the UK. 

Interaction with drug metabolism liquorices, which are the most commonly used herbs in TCM can increase metabolites (e.g., nortriptyline, desipramine, and norclomipramine) of tricyclic antidepressants (TCAs) and may produce more side effects (such as dry mouth, constipation, palpitation, etc.) (Xu, 2004 Zhu Huang, 2004). 

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... 

Although a drug need not be an antidepressant to be more effective than a placebo, it does seem to need sufficient side effects that patients can figure out that they have not been given a placebo. 

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