Antidepressants

What is addiction

An addiction is the continued use of a mood altering substance that can give pleasurable sensations is even though its use becomes compulsive resulting in dependency, loss of control over use of the substance and interference with aspects of life such as work and relationships. With continued use the body becomes tolerant as it adapts to the effects of the addictive substance, which means that more of the substance is needed to give the same reward and this begins the addiction cycle.

Nicotine addiction and dopamine

Nicotine is one of the most addictive drugs and causes a physiological dependency within a very short time after first use. Within seconds of inhalation, nicotine reaches the brain and stimulates release of several neurotransmitters. Nicotine activates the dopamine pathway in the brain by binding to the nicotinic acetylcholine receptor resulting in increased dopamine levels. Dopamine is the neurotransmitter that controls the reward and pleasure centres in the brain and is responsible for reward-driven behaviour. Feelings of pleasure created by dopamine reinforce the behaviour that created the pleasurable feeling, which in the case of nicotine is to continue smoking to be rewarded by the feeling of relaxation and euphoria, which leads to nicotine addiction.

Nicotine stimulates other neurotransmitters, including, noradrenaline that acts as a stimulant increasing heart rate, as well as suppressing appetite; acetylcholine that increases heart rate, muscle movement and cognition, which is why many smokers feel an increase of energy or an increase in ability to concentrate directly after smoking a cigarette. Nicotine also triggers the release of brain endorphin, which is a natural analgesics and “feel good” hormone. Nicotine also increases release of serotonin and when serotonin activity falls, this triggers the craving for another cigarette.

Tolerance and withdrawal

As the effect of nicotine wears off, craving for another cigarette to reinforce the pleasurable feelings associated with nicotine use is triggered. Also more nicotine is needed to achieve the same level of reward. Continued use of nicotine to satisfy the craving leads to tolerance and dependency and so the addiction cycle continues.

If the craving for nicotine is not satisfied the brain reacts to lack of stimulation by nicotine by going into withdrawal and this creates withdrawal symptoms. Symptoms include irritability, restlessness, anxiety, increased appetite, difficulty concentrating, sleep disturbances and constant craving for another cigarette.

Medication for nicotine withdrawal symptoms

Buproprion is an antidepressant drug that acts directly on the brain in a similar way to the SSRI and SNRI antidepressants by increasing the amount of serotonin and noradrenaline, however, but is not selective because it also increases the amount of catecholamines and dopamine. Buproprion also binds to the nicotinic acetylcholine receptor, which blocks the action of nicotine and reduces the reward effects of nicotine. Buproprion is used as part of a smoking cessation programme to help break smoking addiction, by reducing the urge to smoke and counteracting withdrawal symptoms.

Anxiolytic medication

Like all antidepressant drugs, anxiolytic medications act directly at the level of the brain to restore the chemical imbalance that causes symptoms of extreme anxiety.

• Buspirone works by interacting with receptors for the mood enhancing chemical messengers in the brain or neurotransmitters, particularly serotonin and noradrenaline, also dopamine and acetylcholine. Buspirone does not act on receptor sites in the brain that are targets for various sedation-causing drugs like benzodiazepines, barbiturates and inhaled anaesthetics. Therefore buspirone exerts its antianxiety effects without sedation, muscle relaxation, and without compromising mental alertness.


• Tradazone increases the amounts of serotonin and noradrenaline by inhibiting reuptake as well as increasing their activity in the brain. However, it also has sedative properties, by acting on the histamine receptor, which is why it is helpful for treating anxiety.

Symptoms of depression

Depression, also known as clinical depression, major depression or major depressive disorder, is characterised by symptoms including anxiety, loss of interest in activities that are usually pleasurable, disturbed sleep, change in appetite, fatigue, feelings of worthlessness or guilt, difficulty thinking or concentrating, and recurrent thoughts of suicide. If these symptoms continue for more than two weeks this suggests that the depression is a clinical condition and not just feeling low. Once an episode of major depression has occurred there is a high risk of recurrence of another depressive episode. Mood enhancing medications are used to treat depressive episodes and are also used as maintenance against relapse or recurrence of depressive episode.

Mood enhancing neurotransmitters

Serotonin and noradrenaline are the two most important neurotransmitters in the area of the brain that regulates mood. When serotonin or noradrenaline is released from one nerve cell it passes across the gap between nerve cells (synapse) and fires up the next nerve cell. This sets up a communication signal that is transmitted from one nerve cell to another. If there is not sufficient serotonin or noradrenaline released to trigger this nerve signal, then this communication pathway does not work properly and can lead to symptoms of depression.

Inhibition of neurotransmitter reuptake

Both serotonin and noradrenaline are recycled after use by being taken back up into the presynaptic neurone or sending cell. Serotonin noradrenaline reuptake inhibitors (SNRIs) work by inhibiting the reuptake of both serotonin and noradrenaline, whereas the selective serotonin reuptake inhibitors (SSRI) are very selective for serotonin and do not affect other neurotransmitters. SNRIs also have a small effect on other neurotransmitters like dopamine. If neurotransmitter reuptake is inhibited, there is more serotonin or noradrenaline remaining in the synapse to trigger the next cell and continue communication between mood-enhancing neurones.

Tricyclic antidepressants also work by inhibiting neurotransmitter reuptake, however, they non-specific in their action as they also affect several other brain chemicals like histamine and acetylcholine, which accounts for their sedative properties and other side effects.

Reversible inhibitors of monoamine oxidase

Reversible inhibitors of monoamine oxidase (RIMA) antidepressants work by a different mechanism from other classes of antidepressant to boost the amount of mood enhancing neurotransmitters. Once they have done their job by stimulating a nerve impulse, neurotransmitters are removed and one way this is done is by being inactivated by the enzyme monoamine oxidase. Inhibition of monoamine oxidase results in more serotonin and noradrenaline remaining to trigger the next cell and continue communication between mood-enhancing neurones. RIMAs are short lived and their effects reversible so they do not have such serious side effects as earlier drugs.

Bipolar disorder

Bipolar disorder, also known as mania or manic depression, is characterised by episodes of extreme mood swings that alternate between very high excitable mood and very low depression, balanced by periods of “normal mood” in between. These extremes mood swings are thought to be due to over production of excitatory neurotransmitters like serotonin and dopamine.

Reducing neurotransmitter activity

Treatments for bipolar disorder use drugs that work by dampening down excitatory nerve transmission, which is the opposite effect to most antidepressants and has the effect of acting as a mood stabilizer. These drugs include lithium and carbamazepine.

Whereas most antidepressant medication increases the amount of mood enhancing neurotransmitters that cause symptoms of depression when deficient, lithium and carbamazepine work by blocking the action of sodium channels in nerve cell membranes that control the flow of sodium ions, which triggers the nerve cell to send out a nerve impulse. This reduces the release of mood enhancing neurotransmitters like serotonin, noradrenaline and dopamine, and helps prevent the recurrence of severe mood swings after an acute episode as well preventing or reducing the symptoms of mania.