McKenna's Pharmacology for Nursing, 2e

317

C H A P T E R 2 1 Antidepressant agents

W hen you ask people how they feel, they may say “pretty good” or “not so great”. People’s responses are usually appropriate to what is happening in their lives, and they describe themselves as being in a good mood or a bad mood. Some days are better than others. Affect is a term that is used to refer to people’s feelings in response to their environment, whether positive and pleasant or negative and unpleasant. All people experi­ ence different affective states at various times in their lives. These states of mind, which change in particular situations, usually do not last very long and do not often involve extremes of happiness or depression. If a person’s mood goes far beyond the usual normal “ups and downs”, they are said to have an affective disorder. Mental health is a National Priority Area for the Australian Government so is an important area for nurses and midwives to under­ stand and be able to respond to (AIHW, 2013). DEPRESSION AND ANTIDEPRESSANTS Depression is a very common affective disorder involving feelings of sadness that are much more severe and longer lasting than the suspected precipitating event, and the mood of affected individuals is much more intense. The depression may not even be traceable to a specific event or stressor (i.e. there are no external causes). People who are depressed may have little energy, sleep disturb­ ances, lack of appetite, limited libido and inability to perform activities of daily living. They may describe overwhelming feelings of sadness, despair, hopelessness and disorganisation. In many cases, the depression is never diagnosed, and the person is treated for physical manifestations of the underlying disease, such as fatigue, malaise, obesity, anorexia, or alcoholism and drug dependence. Clinical depression is a disorder that can interfere with a person’s family life, job and social interactions. Left untreated, it can produce multiple physical problems that can lead to further depression or, in extreme cases, even suicide. Biogenic amine theory of depression Research on the development of the drugs known to be effective in relieving depression led to formulation of the current hypothesis regarding the cause of depres­ sion. Scientists have theorised that depression results from a deficiency of biogenic amines in key areas of the brain; these biogenic amines include noradrenaline, dopamine and serotonin (5HT). Both noradrenaline and 5HT are released throughout the brain by neurons that react with multiple receptors to regulate arousal, alert­ ness, attention, moods, appetite and sensory processing. Deficiencies of these neurotransmitters may develop for three known reasons. First, monoamine oxidase (MAO) may break them down to be recycled or restored

in the neurons. Second, rapid fire of the neurons may lead to their depletion. Third, the number or sensitivity of postsynaptic receptors may increase, thus depleting neurotransmitter levels. Depression may also occur as a result of other, as yet unknown, causes. This condition may be a syndrome that reflects either activity or lack of activity in a number of sites in the brain, including the arousal centre (reticu­ lar activating system [RAS]), the limbic system and basal ganglia. Drug therapy The use of agents that alter the concentration of neuro­ transmitters in the brain is the most effective means of treating depression with drugs. The antidepressant drugs used today counteract the effects of neurotrans­ mitter deficiencies in three ways. First, they may inhibit the effects of MAO, leading to increased noradrenaline or 5HT in the synaptic cleft. Second, they may block reuptake by the releasing nerve, leading to increased neurotransmitter levels in the synaptic cleft. Third, they may regulate receptor sites and the breakdown of neurotransmitters, leading to an accumulation of neuro­ transmitter in the synaptic cleft. Antidepressants may be classified into three groups: the tricyclic antidepressants (TCAs), the MAO inhibitors and the selective serotonin reuptake inhibitors (SSRIs). Other drugs that are used as antidepressants similarly increase the synaptic cleft concentrations of these neuro­ transmitters (see Figure 21.1). For information on how antidepressants affect people from young to old, see Box 21.1. TRICYCLIC ANTIDEPRESSANTS The tricyclic antidepressants (TCAs) , including the amines, secondary amines and tetracyclics, all reduce the reuptake of 5HT and noradrenaline into nerves. Because all TCAs are similarly effective, the choice of TCA depends on individual response to the drug and tol­ erance of adverse effects. A person who does not respond to one TCA may respond to another drug from this class. TCAs that are available include the amines amitripty­ line ( Endep, Amitrip ), clomipramine ( Anafranil, Placil ), dosulepin hydrochloride, dothiepin ( Dothep ), doxepin ( Deptran , Sinequan ), imipramine ( Tofranil ) and trimi­ pramine ( Surmontil ) and the secondary amines such as nortriptyline ( Allegron ). Table 21.1 shows the relative frequency of the occurrence of adverse effects by specific type of TCA. Therapeutic actions and indications The TCAs inhibit presynaptic reuptake of the neuro­ transmitters 5HT and noradrenaline, which leads to an