Antidepressant drug

Although the drugs included under this general heading have all been used in the treatment of depression, it is important to note that depression is not itself a simple clinical entity and it cannot be easily defined. Depression, associated with emotional excitement and restlessness, is hardly likely to respond to the same agents as does acute melancholia in which all forms of activity, mental and physical, are depressed. Some forms of depression have 

CV//J mephenesin (Myanesin, Myoten, Prolax, Tolserol, Tolulox, etc.) 

The monoamine oxidase inhibitors form yet another group of drugs which were introduced into psychiatry as a result of observations in a different field. It was noticed that tuberculosis patients under treatment with iproniazid frequently became euphoric. The further observation that iproniazid inhibited brain amine oxidase prompted the development of 

The most characteristic (but not completely specific ) pharmacological action of the monoamine oxidase inhibitors is their ability to reverse reserpine sedation and to potentiate the excitatory effects of 5-hydroxtryptamine administration . Given alone, in single doses, they produce no obvious hyperactivity in experimental animals and they may even cause depression. After prolonged administration, sympathetic stimulation and locomotor hyperactivity do occur but these actions are still not so marked as when the inhibitors are administered in conjunction with 5-HTP. The physiological significance of this observation has been discussed earlier (p. 269). 

Some of the monoamine oxidase inhibitors prolong the hexobarbitone sleeping time in mice, probably because they inhibit barbiturate breakdown by the liver microsomes . An anticonvulsive action has also been reported . The fact that the hydrazine derivatives interact with pyridoxal phosphate and can thus inhibit GABA formation may explain why some of the inhibitors of this type sometimes have a convulsive action also. 

Reports are on hand relating to more recent antidepressants such as bupropion, citalopram (Fairweather ei ul., 1997), fluoxetine (Gelfin et ul.. 1998). moclobemide (Dingemanse et ul., 1998) and paroxetine (Brauer et ul.. 1995). These products, in agreement with their clinical profiles, produce fewer subjective effects and generally less sedation in healthy subjects than the older 

Area of assessment Clinically sedative antidepressants, e.g. amitriptyline, mianserin, trimipramine Less sedative antidepressants, e.g. bupropion, fluoxetin, moclobemide, nefazodone  

Subjective Relaxation, Drowsiness, No effect Weak effects if 

Learning, memory Weak effects if any Some impairment Enhanced long-term memory No effect 

On the other hand, it has been suggested that the primary problem in depression is an increased sensitivity to receptors that are located on the presynaptic terminals of amine synapses.54 These presynaptic autoreceptors normally regulate and limit the release of amine transmitters, such as norepinephrine or serotonin, from the presynaptic terminal. Increasing their sensitivity could result in a relative lack of adequate neurotransmitter release at these synapses. By causing overstimulation of these presynaptic receptors, antidepressant drugs could eventually normalize their sensitivity and help reestablish proper control and regulation of these amine synapses.54 

Tricyclics. Drugs in this category share a common three-ring chemical structure (hence the name tricyclic ). These drugs work by blocking the reuptake of amine neurotransmitters into the presynaptic terminal.61,67 Actively transporting amine neurotransmitters back into the presynaptic terminal is the method by which most (50 to 80 percent) of the released transmitter is removed from the synaptic cleft. By blocking reuptake, tricyclics allow the released amines to 

Generic Name Trade Name Initial Adult Dose (mg/day) Prescribing Limits (mg/day) 

FIGURE 7-2 T Effects of antidepressant drugs on amine synapses. All three types of drugs 

In the past, tricyclic drugs such as amitriptyline and nortriptyline were the most commonly used antidepressants and were the standard against which other antidepressants were measured.30 The use of tricyclic drugs as the initial treatment of depression has diminished somewhat in favor of some of the newer second-generation drugs, which may have more favorable side-effect profiles. Tricyclic agents, nonetheless, remain an important component in the management of depressive disorders, especially in more severe forms of depression that fail to respond to other antidepressants.6,53 

Depression is one of the most common psychiatric disorders. It is characterized by feeling of intense sadness, helplessness, worthlessness, and impaired functioning. Those experiencing a major depressive episode exhibit physical and psychological symptoms, such as appetite disturbances, sleep disturbances, and loss of interest in job, family, and other activities usually enjoyed. A major depressive episode is a depressed or dysphoric (extreme or exaggerated sadness, anxiety, or unhappiness) mood that interferes with daily functioning and includes five or more of the symptoms listed in Display 31-1. 

To be classified as a major depression, these symptoms should occur daily or nearly every day for a period of 2 weeks or more. The symptoms of major depression should not be the result of normal bereavement, such as the loss of a loved one, or disease, such as hypothyroidism. 

Depression is treated with the use of antidepressan t drugs. Psychotherapy is used in conjunction with the antidepressant drug s in treating major depressive episodes. The four types of antidepressants are  

The TCAs, such as amitriptyline (Elavil) and dox-epin (Sinequan), inhibit reuptake of norepinephrine or serotonin at the presynaptic neuron. Drug classified as MAOIs inhibit the activity of monoamine oxidase a complex enzyme system that is responsible for breaking down amines. This results in an increase in endogenous epinephrine, norepinephrine and serotonin in the nervous system. An increase in these neurohormones results in stimulation of the CNS. The action of the SSRIs is linked to their inhibition of CNS neuronal uptake of serotonin (a CNS neurotransmitter). The increase in serotonin levels is thought to act as a stimulant to reverse depression. 

The mechanism of action of most of the miscellaneous antidepressants is not clearly understood. Examples of this group of drugs include fluoxetine (Prozac) and bupropion (Wellbutrin). 

Schematic classification according to main mode of therapeutic action 

Legend Inhibition MAO MAOl Monamine oxidase MAO inhibitor 

As a rule of thumb, all antidepressant drugs have comparable efficacy but different adverse effects profiles, although there are a few exceptions to this (e.g. selective serotonin reuptake inhibitors (SSRIs) are less efficacious in severe major depressive disorder). 

The antidepressants can be classified according to their mechanism of action, specifically  

By blocking MAO, the excess neurotransmitters are stored and released again upon need.  

Diminished interest in adivitiesof life Significant weight loss or gain (without dieting) 

Insomnia (inability to sleep) or hypersomnia (excessive sleeping) 

Recurrent thoughts of death or suidde (or suidde attempt) 

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Fluoxetine hydrochloride (Prozac) is a widely prescribed antidepressant drug introduced by Eh Lilly Co in 1986 It differs from Compound A in having an —NHCH3 group in place of —N(CH3)2 What IS the structure of Prozac" ... 

Description of Method. Fluoxetine, whose structure is shown in Figure 12.31a, is another name for the antidepressant drug Prozac. The determination of fluoxetine and its metabolite norfluoxetine. Figure 12.31 b, in serum is an important part of monitoring its therapeutic use. The analysis is complicated by the complex matrix of serum samples. A solid-phase extraction followed by an HPLC analysis using a fluorescence detector provides the necessary selectivity and detection limits. 

Almost anyone who has at some time in his life met some reverses is familiar with depression. In the normal course of events, changing circumstances will soon lead to the replacement of this state of mind by a more pleasant one. There exist, however, a set of pathologic states in which depression feeds on itself in a destructive cycle. Individuals affected with this syndrome— whether precipitated by outside events or not—eventually find it most difficult to function. The advent of antidepressant drugs, first the MAO inhibitors and more recently the tricyclic antidepressants, have made this syndrome amenable to treatment. 

The widely used tricyclic antidepressant drugs such as imipramine and amitriptyptiline have in common a series of... 

S. Ulrich and J. Maitens, Solid-phase microextraction with capillai y gas-liquid cliro-matography and niti ogen-phosphoi us selective detection foi the assay of antidepressant drugs in human plasma , J. Chromatogr. B 696 217-234 (1997). 

Like the Hofmann rearrangement, the Curtius rearrangement is often used commercially. For example, the antidepressant drug tranylcypromine is made by Curtius rearrangement of 2-phenylcyclopropanecarbonyl chloride. 

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],... 

Discuss the uses, general drug actions, general adverse reactions, contraindications, precautions, and interactions of the antidepressant drugs. 

Discuss important preadministration and ongoing assessment activities that the nurse should perform on the patient taking antidepressant drugs. 

Discuss ways to promote an optimal response to therapy, how to manage common adverse reactions, and important points to keep in mind when educating patients about the use of antidepressant drugs. 

Antidepressant drugs are used to manage depressive episodes such as major depression or depression accompanied by anxiety. These drugs may be used in conjunction with psychotherapy in severe depression. The SSRIs also are used to treat obsessive-compulsive disorders. The uses of individual antidepressants are given in the Summary Drug Table Antidepressants. Treatment is usually continued for 9 months after recovery from the first major depressive episode. If the patient, at a later date, experiences another major depressive episode, treatment is continued for 5 years, and with a third episode, treatment is continued indefinitely. 

The nurse explains any adverse reactions tiiat may occur widi a specific antidepressant drug and encourages the patient or family member to contact die primary healdi care provider immediately if a serious drug reaction occurs. 

Promoting Patient Responsibility for Antidepressant Drug Therapy... 

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