Major Depression

TREATMENT

Depression is treatable and needs to be treated yet many who are depressed are not treated, or if treated, are under - treated. You can't will depression away or hope that time alone will see depression disappear - it doesn't. If you are depressed, be bold and kind to yourself by seeking treatment. Today, prospects for successful treatment have never been as great, enabling life to be restored and renewing opportunities to prosper. If the diagnosis of depression is confirmed and treatment is commenced, specific actions self - initiated are also helpful in facilitating recovery; such actions are listed in Table 8.

DRUG ASSISTED TREATMENTS

Today, treatment of major depression with antidepressants is becoming the norm. Due to spectacular progress into understanding the brain chemistry underlying depression, medications are now available that have remarkable benefits in minimising the symptoms and reducing impairment.

HOW DO ANTIDEPRESSANTS WORK?

Understanding how antidepressants work requires knowing how messages travel in the brain. There are more cells in the brain than people on earth. IMAGINE! One hundred billion of these cells are called neurons that interconnect in complex networks. A simplified drawing of a neuron is shown in Figure 1.

Figure 1. Diagram of a neuron

The anatomy of neurons that distinguishes them from other cell types is the dendrites and axons attached to the cell body. These structures enable neurons to communicate. Dendrites receive signals from other neurons and transmit electrical messages into the cell body. Axons and their branches conduct signals away from the cell body.

The protrusions at the tip of the axon known as synaptic terminals contain neurotransmitters in vesicles. Separating the synaptic terminals and the receiving dendrites is a space known as the synaptic cleft. (See Figure 2.) Messages that travel down the axon are electrical; those that travel across the synaptic cleft are chemical and known as neurotransmitters.

Figure 2. Diagram of a neurotransmitter travelling across the synapse to the postsynaptic receptor

The most common neurotransmitters are serotonin, noradrenaline and dopamine, which when released from the transmitting neuron, travel across the synaptic cleft and dock onto the receptors of the receiving dendrites. These receptors are known as the postsynaptic receptors. Once occupied, these receptors enable the message to continue. After docking, the neurotransmitter will either be rapidly released into the synaptic cleft where it may be absorbed into the transmitting neuron through a reuptake pump for later use or be destroyed by enzymes in the synaptic cleft. Once the receptors are occupied, cascades of chemical reactions occur within the receiving neuron enabling continued transmission of the neural-messages. Eventually these messages result in genes found in the nucleus to be switched on or off, an effect that may impact upon the functioning of the entire neuron and its ability to communicate and interact with other neurons in the brain.

A hypothesis, known as the monoamine hypothesis, suggests that depression arises when neurotransmitters fail to trigger an adequate signal at the postsynaptic receptors. Antidepressants work by either enhancing the release of the neurotransmitters from the transmitting neuron or inhibiting the reuptake of the neurotransmitters from the synaptic cleft. Both actions enable the neurotransmitters to be more available at the postsynaptic receptors, enhancing the chances for the signal to be transmitted.

Recently the monoamine hypothesis has been challenged by the stress hypothesis, which suggests that the onset of depression stems from a disruption of the bodies stress mechanisms that impacts upon brain functioning. Simply put, stress can lead to depression.

TYPES OF ANTIDEPRESSANTS

Today there are eight classes of antidepressants. Each class has a slightly different mode of action but each class enhances neurotransmitter function. Table 9 shows each class of antidepressants and the daily dose range.

Over the last twenty - five years, knowledge of the neurotransmitter function has triggered the production of new antidepressants, which provide a more specific mode of action, safety and tolerability. They are uniquely different from the first antidepressants of forty years ago, known as the first generation antidepressants that had broad and non - specific actions in enhancing neurotransmitter function. While the first generation antidepressants are effective in treating depression, they have hazardous adverse side effects. For example, the tricyclic antidepressants are lethal in an overdose and the MAOs require a Tyramine free diet to avoid a hypertensive episode. Today, these antidepressants are used less frequently.

The second - generation antidepressants appeared in the 1980s and included the selective serotonin reuptake inhibitors (SSRIs), Mianserin and Moclobmide. These medications are more specific in action and better tolerated than the first generation antidepressants. The SSRIs are currently the most widely used class of antidepressants, and are not considered lethal in overdose. They act specifically in inhibiting the reuptake of serotonin from the synaptic cleft.

In the last decade, a third generation of antidepressants has been marketed that has multiple but specific modes of action. In contrast to the first generation of antidepressants, the second and third generations appear to be effective in treating the co - occurring anxiety disorders. Will there be a fourth generation of antidepressants? The answer is yes. The antidepressants that are presently being tested have mechanisms of action quite different from those of earlier generations. Hopefully, the fourth generation antidepressants will bring relief to those who are presently resistant to current treatment. Studies show that no generation of antidepressant is more effective, however, the antidepressants in the second and third generation have less side effects and are thus better tolerated. When there is better tolerance, effectiveness is enhanced, as the antidepressants are more likely to be taken for the full treatment period, a factor that reduces the risk of relapse.

TAKING ANTIDEPRESSANTS

Treatment with antidepressants commences with a low dose that is increased overtime until symptoms remit. While most who are depressed want a "quick fix", antidepressants unfortunately take time to have their effect. Most antidepressants require two to four weeks for their therapeutic effect to be felt. In contrast, side effects are felt immediately but often resolve overtime. For some, the initial antidepressant may be without effect or cause intolerable side effects. These factors necessitate switching to another antidepressant perhaps from a different class. It has been shown that one in three do not respond to the first antidepressant.

Optimal treatment with antidepressants is attained through regular monitoring of the status of your depressive symptoms by a health care provider. To aid monitoring, l encourage all to self - monitor, recording mood twice daily between (7am to 7pm) on a 1 to 10 scale, 10 being happy and 1 being depressed. Twice daily monitoring is necessary to obtain a record of daily mood fluctuations that often occurs. Lowered mood is experienced by some in the morning with the mood improving as the day progresses. For others, the mood fluctuation is the opposite.

It is your responsibility when taking antidepressants to be aware of their potential side effects and to report them to your health care provider. Most side effects are transient and harmless, however, for some they persist and cannot be tolerated. When this situation arises discuss your predicament with your health care provider, don't just stop taking the antidepressant.

Antidepressants ought to be taken at the same time each day enabling a steady blood level of the drug to be maintained. It has been shown that a relatively steady state of the antidepressant in the blood stream enhances its effectiveness. Most who take antidepressants ask the question, "are antidepressants addictive?" The answer is a definite NO. Once the depression has remitted, there is often no need to further increase the dose. At times, however the antidepressant may need to be increased if the symptoms re-emerge, this may occur in times of stress.

Discontinuing antidepressant therapy is a decision that needs to occur in consultation with your health care provider. Factors that will influence the decision are your current mood, the severity of previous depressive episodes, the likelihood of a relapse or reoccurrence and the risk of suicide. If discontinuation is initiated, a slow taper is the norm particularly where higher doses have been used over an extended time. If antidepressants have been used for six to eight months, a taper period of six to eight weeks is suggested. However, in contrast, when the antidepressant has been used on a maintenance regime, a three to six month period of withdrawal is required. The physical and psychological symptoms associated with discontinuation usually occur within one to ten days of cessation. Unfortunately, for some, the discontinuation of antidepressants results in return of symptoms of depression following the withdrawal phase, for others, depressive symptoms never return.

How long should one stay on antidepressants? Some consider stopping their antidepressant as soon as they feel well. This often results in a rapid return of the depressive symptoms. It is suggested that one should use antidepressants for eight to twelve months followed by a discontinuation using a slow tapering off.

PHYSICAL TREATMENTS FOR MAJOR DEPRESSION

Electro-convulsive therapy (ECT)

Today, ECT is used in the treatment of depression where there is a resistance to other treatments, where hallucinations or delusions co-occur, when antidepressants cannot be used and when the sufferer is acutely suicidal. ECT has a higher rate of success than any other form of treatment for depression. Moreover, it has a more rapid onset of action than antidepressants.

ECT may be administered with or without the simultaneous use of antidepressants.ECT is administered in the early morning after eight to twelve hours of fasting. Administration occurs three times weekly. Initially, three to six treatments are administered, if required, the number of treatments is increased. Prior to treatment, sedation is induced and a muscle relaxant administered. The brain is then stimulated via a small current passed through the brain activating and producing a seizure. The electrodes are placed above the temple on the non-dominant side of the brain (unilateral ECT) or one electrode is placed above each temple (bilateral ECT). The duration of seizures is thirty seconds to one minute with the patient awakening ten to fifteen minutes later. For some who receive ECT, short-term memory loss is experienced that may last for a few days post treatment and disappear within several months.

PHYSICAL TREATMENTS CURRENTLY BEING INVESTIGATED

Vagus nerve stimulation (VNS)

Vagus Nerve Stimulation (VNS) may become an alternative to ECT in the treatment of depression. This mode of treatment involves electrical stimulation of the vagus nerve, one of twelve pairs of cranial nerves that originate in the brain. This nerve functions like a super highway, transmitting messages to and from the brain and vital body organs including the stomach and the heart. Treatment involves implanting a transmitter into the upper area of the chest with a connecting wire from the device to the vagus nerve in the neck. The vagus nerve carries the signals from the generator into the brain. A thirty second impulse is transmitted every thirty seconds with 80% of the signals reaching and activating those areas of the brain involved in the regulation of mood disorders. To date, this mode of treatment is in its experimental phase but results are promising.

Trans-magnetic stimulation (TMS)

Trans – magnetic stimulation (TMS), also an alternative to ECT, is emerging to be effective in the treatment of depression. This technique is based on the observations of Michael Faraday, an English chemical physicist (1791 – 1861), who observed that electrical energy could be converted into magnetic fields and vice versa. This therapy involves placing an electromagnetic coil close to the head through which time-varying electrical charges are passed. The outcome of this treatment is that its magnetic fields produce a magnetic field that passes unencumbered by the base of the scull inducing an electrical current and stimulating cortical neurons. Studies suggest that TMS is safe.

PSYCHOLOGICAL THERAPIES

The two most utilised psychological therapies in the treatment of major depression are interpersonal psychotherapy and cognitive behavioural therapy (CBT).

Interpersonal psychotherapy

This therapy is brief, highly structured and deals with interpersonal issues in depression, particularly the impact the illness has on relationships. It also deals with adapting to the changing circumstances of life resulting from the illness, the handling of grief and overcoming periods of interpersonal impoverishment in relationships, which may have occurred prior, while or during the depression. This therapy is twelve to sixteen one - hour sessions, the initial sessions are involved in fact finding and the remaining sessions address issues. Today, the efficacy of this therapy in the treatment of depression is being questioned.

Cognitive Behavioural Therapy (CBT)

Cognitive behavioural therapy (CBT) is the most widely used psychological therapy in the treatment of depression and is often considered by its practitioners to be a panacea to all, however, it is not. Recent studies show that CBT used alone is not as efficacious in the treatment of major depression as previously thought. If CBT is to be used, it ought to be used as an adjunct to pharmacotherapy and its effectiveness monitored. It is pertinent to view CBT as two modes of therapy, that is, cognitive therapy and behavioural therapy; both therapies can be used alone or simultaneously.

· Cognitive therapy

Cognitive therapy is based on the findings that thoughts and feelings are closely connected and that thoughts influence feelings, therefore, changing thoughts would change feelings. This therapy encourages self-awareness of the occurring maladaptive thinking patterns that sustain depression. Examples of such thoughts are listed in Table 10. Cognitive therapy requires recognition of the maladaptive thoughts, which are frequently manifested in distressing automatic thought patterns and focus on catastrophic or negative outcomes. Recognition is followed via challenging the thoughts by asking the question,"what is the evidence for the thought”. In the absence of evidence, a more functional thought is established.

· Behavioural therapy

Behaviour therapy aims to stimulate recovery, prevent relapse and to overcome socio -economic changes stemming from the illness. Programs are initiated that facilitate development of a healthy lifestyle, reducing stress and overcoming situations previously feared. Goals for the future are established with pathways set to achieve these goals. The importance of taking control of one’s present and future life is emphasised as those with depression often feel a sense of helplessness.

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