Treating depression
- Write an essay entitled “Treating depression”
- Give an account of the link between stress, anxiety and depression and the therapeutic drugs used to treat these disorders
Stress is usually a precursor to anxiety and depression. Depression is the most common of the affective disorder, that affecting the mood rather than disturbances of thought or cognition. Most people experience a brief period of depression, usually attributed to a particular circumstances (normal). Pathological state is distinguished from normal sadness because of its duration (at least 10-14 days of continuous or almost continuous presence of these emotional difficulties). Without treatment, symptoms can last for weeks, months, or years
In depression, the hypothalamic-pituitary-adrenal (HPA) axis is upregulated with a down-regulation of its negative feedback controls. Corticotropin-releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocorticotropin hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands; adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol receptors become desensitized leading to increased activity of the pro-inflammatory immune mediators and disturbances in neurotransmitter transmission.
The main types of Antidepressant drugs are:
- Monoamine oxidase inhibitors (MAO)
- Tricyclic antidepressants (TCAs) – monoamine uptake inhibitors:
- selective 5-HT (serotonin) reuptake inhibitors (SSRI) (are the most widely prescribed agents)
- Serotonin and noradrenalin reuptake inhibitors (SNRI)[unique_solution]
- Miscellaneous antidepressants:
non-selective receptor blocking effects, mechanism of action poorly understood
All target the monoamine pathways.
Evidence from double blind placebo controlled trials showed that anti-depressants are effective in alleviating symptoms in 65-75% of patients compared to a placebo response rate of 35%.
MAO inhibitors
Include inhibition of MAO-A and or MAO-B. These drugs are irreversible – last for several weeks. They are administered orally, and readily absorbed in GI tract. They are Increase 5-HT, NA and dopamine in the brain, blood, heart and intestine. In normal subjects, MAO inhibitors cause an immediate increase in motor activity – euphoria and excitement develop over the course of a few days. MAO-A inhibitors act to deaminate 5-HT, NA, adrenalin, dopamine. While MAO-B inhibitors deaminates dopamine, tyramine, phenylethylamine. MAO-B inhibitors restore dopamine levels to within the normal range in depressed individuals.
S.E/ Due to over-activity of catecholamine system: Weight gain, Hypotension, Sexual dysfunction and CNS stimulation – restlessness, insomnia, tremors. Acute overdose causes CNS stimulation, sometimes convulsions. Also, Severe hypertensive response to tyramine-containing foods (‘cheese reaction’), tyramines displaces NA from sympathetic nerve terminals – increase in blood pressure.
Tricyclic antidepressant drugs (TCAs): (a.k.a. Uptake-1 inhibitors)
They are well absorbed orally, and they bind to re-uptake transporters preventing re-uptake and subsequent degradation of 5-HT and NA. They increase the concentration of monoamines in extracellular space, and prolonged duration of transmitter action at synapse. They Improve emotional symptoms – 5-HT-mediated transmission, and relief of biological symptoms – NA-mediated transmission.
S.E/ Normal clinical dose: sedation (blockade of histamine receptors), drowsiness , difficulty in concentrating, dry mouth, blurred vision, constipation and urinary retention (blockade of muscarinic receptors), dizziness, postural hypotension (blockade of a-adrenoceptors), potentiate the depressant effects of alcohol, nervousness and insomnia. In overdose: ventricular dysrhythmias and potential heart failure
Selective serotonin uptake inhibitors (SSRI):
Currently, the most commonly prescribed antidepressants. Drugs that selectively inhibit 5-HT (serotonin) uptake, and they are well absorbed orally and have plasma t1/2 15-24 h. They are as effective as TCA and MAOI in treating depression of moderate degree but probably less effective in treating severe depression. For example, Fluoxetine (Prozac) is currently the most prescribed antidepressant (also used for anxiety, panic disorders, OCD, appetite suppressant).
S.E/ Nausea, Insomnia, Sexual dysfunction, No food reactions but dangerous ‘serotonin reaction’ (hyperthermia, muscle rigidity, cardiovascular collapse) can occur if given with MAOI. They are less likely than TCA to cause anti-cholinergic side-effects and are less dangerous in overdose
Selective noradrenaline re-uptake inhibitors (NARIs)
This action of NARIs is though to contribute to the alleviation of the symptoms of depression. In the presence of the NARI, small amounts of noradrenaline continue to be degraded in the synaptic cleft.
leads to the accumulation of NA in the synaptic cleft and return to concentrations within the normal range
St John’s wort
Taking St John’s wort with other medications, such as anticonvulsants, anticoagulants, antidepressants and the contraceptive pill, can also cause serious problems.
Researchers have discovered a biological link between stress, anxiety and depression.
By identifying the connecting mechanism in the brain, the researchers show exactly how stress and anxiety could lead to depression.
The linking mechanism in the study involves the interaction between corticotropin releasing factor receptor 1 (CRFR1) and specific types of serotonin receptors (5-HTRs). While no one has been able to connect these two receptors on a molecular level, the study reveals that CRFR1 works to increase the number of 5-HTRs on cell surfaces in the brain, which can cause abnormal brain signaling. Since CRFR1 activation leads to anxiety in response to stress, and 5-HTRs lead to depression, the research shows how stress, anxiety and depression pathways connect through distinct processes in the brain. Most importantly, the inhibitor developed by the Ferguson lab blocks 5-HTRs in the pathway to combat anxious behaviour, and potentially depression, in mice.
While major depressive disorder often occurs together with anxiety disorder in patients, the causes for both are strongly linked to stressful experiences. Stressful experiences can also make the symptoms of anxiety and depression more severe. By discovering and then blocking a pathway responsible for the link between stress, anxiety and depression, Ferguson not only provides the first biological evidence for a connection, but he also pioneers the development of a potential drug for more effective treatment.
The Link Between Anxiety and Depression Disorder
Anxiety and depression disorders are not the same although there are similar elements. Depression generates emotions such as hopelessness, despair and anger. Energy levels are usually very low, and depressed people often feel overwhelmed by the day-to-day tasks and personal relationships so essential to life.
A person with anxiety disorder, however, experiences fear, panic or anxiety in situations where most people would not feel anxious or threatened. The sufferer may experience sudden panic or anxiety attacks without any recognized trigger, and often lives with a constant nagging worry or anxiousness. Without treatment, anxiety and depression disorders can restrict a person’s ability to work, maintain relationships, or even leave the house.
Both anxiety and depression treatment are similar, which may explain why the two disorders are so often confused. Antidepressant medication is often used for anxiety and depression and behavioral therapy frequently helps people overcome both conditions.
Why Are Depression and Anxiety Linked?
Although no one knows exactly why, depression and anxiety often occur together. In one study, 85% of those with major depression were also diagnosed with generalized anxiety disorder and 35% had symptoms of panic disorder. Other anxiety disorders include obsessive-compulsive disorder and post-traumatic stress disorder (PTSD). Because they so often go hand in hand, anxiety and depression are considered the fraternal twins of mood disorders.
Believed to be caused in part by a malfunction of brain chemistry, generalized anxiety is not the normal apprehension one feels before taking a test or awaiting the outcome of a biopsy. A person with an anxiety disorder suffers from what President Franklin Roosevelt called “fear itself.” For a reason that is only partially known, the brain’s fight-or-flight mechanism becomes activated, even when no real threat exists. Being chronically anxious is like being stalked by an imaginary tiger. The feeling of being in danger never goes away.
“Even more than the depression, it was my anxiety and agitation that became the defining symptoms of my illness. Like epileptic seizures, a series of frenzied anxiety attacks would descend upon me without warning. My body was possessed by a chaotic, demonic force which led to my shaking, pacing and violently hitting myself across the chest or in the head. This self-flagellation seemed to provide a physical outlet for my invisible torment, as if I were letting steam out of a pressure cooker.” ~ Douglas Bloch, M.A., author of “Healing From Depression”
When Anxiety and Depression Occur Together
Being both anxious and depressed is a tremendous challenge. Clinicians have observed when anxiety occurs comorbidly (together) with depression, the symptoms of both depression and anxiety are more severe compared to when each disorder occursalone. Moreover, the symptoms of depression take longer to resolve, making the illness more chronic and more resistant to treatment (read more about: Depression Treatment).
Finally, depression exacerbated by anxiety has a much higher suicide rate than depression alone. In one study, 92% of depressed patients who had attempted suicide were also plagued by severe anxiety.1 Like alcohol and barbiturates, depression and anxiety are a deadly combination when taken together.