Treatments

 The use of treatments has dramatically reduced the remission rate of unipolar depression to 17%, however in the absence of these treatments depression has been reported to remit in 50% of cases with a 70% likelihood of remission amongst individuals who have experienced 3 or more episodes of depression.

There are three major forms of depression these include the following:

·         Medication

·          Psychotherapy

·          Electroconvulsive therapy

With greater understanding and knowledge of molecular interactions within the brain researchers have created drugs with greater specificity in treating depression, for this reason drugs have been used more commonly amongst developed societies as a primary form of treating depression.

Antidepressants are helpful in reducing unipolar depression symptoms, if taken at the right dose for the recommended length of time which is usually between 4-6 weeks (however evidence have shown venlafaxine has a greater efficacy at doses of 150mg or greater.

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The diverse forms of antidepressants fall in the following groups:

·         Monoamine oxidase inhibitors (MAOI)

·         Inhibitors of monoamine uptake

·         Atypical receptor-blocking compounds

Monoamine oxidase inhibitors (MAOI)

Class of antidepressant	Examples
Non-competitive irreversible blockers of MAO-A and MOA-B	Phenelzine, Tranylcypromine, Isocarboxazid
Reversible, MAO-A selective inhibitors	Moclobemide

 Monoamine oxidase inhibitors (MAOI) mechanism of actions

Monoamines oxidases are enzymes, which consists of the two isoforms MAO-A and MOA-B, which differ according to the substrate they bind to. These enzymes are present in neurones and metabolise the monoamines within the neurones. However inhibition of MAO-A correlates better with antidpressants efficacy.

Side-effects- Dietary interactions could possibly occur such as ‘cheese reaction’. Usually, MAO in the gut wall and liver function to break down ingested tyramine. However, when this enzyme reaches the blood circulation it stimulates the release of noradrenaline from the sympathetic nerve terminals that consequently results in a rise in blood pressure. For this reason depressed individuals administrated with MAOI are advised to avoid foods rich in tryamine (these include cheese and alcoholic drinks).Cough mixtures and nasal decongestants, which contain sympathomimetic amines, have also been advised to avoid. 

Due to the unspecific actions of the MAOI they reduce the metabolism of barbiturates, opioids and alcohol. Side effects associated with MAOI include:

·         CNS stimulation resulting in excitement and tremor.

·         Sympathetic blockade leading to postural hypotension.

·         Blurred vision and dry mouth associated with muscarnic blockade.

·         Phenelzine is also assumed to have hepatotoxic effects.

Inhibitors of monoamine uptake

Class of antidepressant	Examples
Non-selective noradrenaline-serotonin uptake inhibitors	Tricyclic antidepressants (TCA) ·         Imipramine ·         Amitriptyline ·         Lofepramine Venelafaxine-although slightly more selective for serotonin than noradrenaline
Selective-serotonin reuptake inhibitor (SSRI)	Fluoxetine (Prozac), Fluvoxamine, Paroxetine and Sertaline

 

Non-selective noradrenaline-serotonin uptake inhibitors mechanisms of action

These drugs specifically block serotonin and noradrenaline uptake into presynaptic terminals from the synaptic cleft, consequently cause potentiation of neurotransmitter activity in the CNS. They express high affinities for H₁ and muscarinic receptors and for a₁ and a₂ receptors. These drug interactions are similar to those present amongst selective serotonin reuptake inhibitors. Amongst the TCA group all the drugs have reported to have similar antidepressant activities and therefore the choice of the drug is dependent upon the most acceptable or most desired side effects. For instance individuals suffering from agitated or anxious states are recommended to take drugs such as amitriptyline or trimipramine based on their sedative actions. Recent therapeutic drugs such as lofepramine have been favourable as they produce fewer antimuscarinic side effects. 

Contraindication-These drugs should not be used in patients who are suffering from the following:

·         Manic phase

·         Severe liver disease

·         Recent myocardial infarction/arrhythmias especially heart blockers (as TCA enhance the risks of conduction abnormalities).

·         Patients taking anticholinergic drugs, alcohol and adrenaline (as TCA potentiates these effects.

Venlafaxine should be taken with caution within hypertensive patients, as this drug is known to raise blood pressure. 

Side effects-Although drugs such as TCA and their related drugs are reported as good approaches in alleviate depression they produce adverse side effects, which can reduce a patients compliance and acceptability. These drugs produce the following complications:

·         Dry mouth, blurred vision and constipation due to muscarinic blocking.

·         Postural hypotension, as a result of alpha-adrenergic blocking effects.

·         Weight increases.

·         Increasing likelihood of suffering from arrhythmias due to the noradrenaline uptake block present in the heart.

·         Sedation due to histamine-blocking

Due to the cardiotoxic nature of these drugs, they are capable of producing adverse effects such as confusion, mania and potentially fatal arrhythmias. Consequently overdose of drugs such as TCA are potentially dangerous.

Although venlafaxine have similar pharmaceutical mechanisms to TCA their expression of a lower affinity for cholinergic, histaminergic receptors and

a-adrenorecptor results in fewer side effects in comparison to TCA.

Venlafaxine have similar drug actions to non-selective noradrenaline-serotonin uptake inhibitors, however these effects occur at a lower frequency.

      

Selective serotonin reuptake inhibitor mechanisms of action

 These are one of the most recently introduced classes of antidepressants. Which have specificity for potent inhibition of serotonin reuptake into nerve terminals from the synaptic cleft, while having minimum effects on noradrenaline uptake. These blocked serotonin transporters belong to a class of Na⁺/Cl^- coupled transporters.

Contraindications-These drugs may cause potentially fatal serotonergic syndrome of hyperthermia and cardiovascular collapses if used in conjunction with MAOI’s.

Side effects-Due to no amine interaction, anticholinergic action, adrenergic blockade or toxic effect associated with an overdose these drugs are known to produce less severe side effects in comparison to TCA and MAOIs.

Atypical receptor-blocking compounds

Class of antidepressant	Examples
Group of drugs whose mechanisms are poorly understood	Mianserin Trazodone Mirtazapine Hyperforin Reboxetine

 Atypical receptor-blocking compounds mechanism of action

Drugs such as Reboxetine are noradrenaline reuptake inhibitors resulting in an increasing concentration of noradrenaline in the synaptic cleft. Other drugs such as Mirtazepine acts on inhibitory a₂- autoreceptors through central noradrenergic nerve terminals by blocking a₂-autoreceptors.

Contraindications -These are similar to TCA.

Side effects -This class of drugs produces fewer side effects as a result of overdose; they also cause less autonomic side effects. Mirtazapine tranquillizer and is therefore administrated to patients who show symptoms such as agitation.

Although these drugs have been proven to be very useful in treating unipolar depression the most effective method in alleviating depression is through the combination of psychotherapy and drug treatment. Psychotherapy treatments in the form of cognitive behavioural therapy have been proven to be more effective in treating unipolar depression amongst elderly depressed individuals.

Treatments such as Electroconvulsive therapy  have been effective in treating serve forms of unipolar depression. Here two electrodes are placed on the brain and send pulses of electrical activity.