ANTIDEPRESSANTS
Affective disorders involve a disturbance of mood (cognitive/emotional symptoms)
associated with changes in behaviour, energy, appetite and sleep (biological
symptoms).
Affective disorders can be thought of as pathological extremes of the normal
continuum of human moods, from extreme excitement and elation (mania) to severe
depressive states.
There are two types of affective disorder: unipolar affective disorders and bipolar
affective disorders.
Unipolar affective disorders (about 80% of depressed cases) in which the
mood swings in one direction only (a feeling of depression only)
Bipolar affective disorders (or maniac depressive psychoses, MDP)
characterised by cyclic manifestation of depression followed by mania (20%
of cases)
Monoamine theory of depression
Genetic, environmental and neurochemical influences have all been examined as possible
aetiological factors. The most widely accepted neurochemical explanation of endogenous
depression involves the monoamines (noradrenaline; serotonin (5-HT); dopamine). The
original hypothesis of depression, ‘the monoamine theory’, stated that depression resulted
from a functional deficit of these transmitter amines, whereas conversely mania was caused
by an excess.
The monoamine theory explains why:
Drugs that deplete monoamines are depressant, e.g. reserpine and methyldopa.
A wide range of drugs that increase the functional availability of monoamine
neurotransmitters improve mood in depressed patients, e.g. tricyclic
antidepressants (TCAs) and MAO inhibitors. The concentration of
monoamines and their metabolites is reduced in the cerebrospinal fluid (CSF)
of depressed patients.
, In some post-mortem studies the most consistent finding is an elevation in
cortical 5-HT2 binding.
The monoamine theory cannot explain why:
A number of compounds that increase the functional availability of
monoamines, e.g. amphetamines, cocaine and L-dopa, have no effect on the
mood of depressed patients.
Some older, atypical anti depressants e.g.iprindole, worked without
manipulating monoaminergic systems.
There is a ‘therapeutic delay’ of 2 weeks between the full neurochemical
effects of antidepressants and the start of their therapeutic effect.
It is unlikely, therefore, that monoamine mechanisms alone are responsible for
the symptoms of depression.
Other systems that may be involved in depression include:
The GABA system
The neuropeptide systems, particularly vasopressin and the endogenous opiates
Secondary-messenger systems also appear to have a crucial role in some
treatments.
Unipolar affective disorders
A common unipolar affective disorder is depression, which is characterized by
misery, malaise, despair, guilt, apathy, indecisiveness, low energy and fatigue,
changes in sleeping pattern, loss of appetite and suicidal thoughts.
Attempts have been made to classify types of depression as either ‘reactive’ or
‘endogenous’ in origin. Reactive depression is where there is a clear psychological
cause, e.g. bereavement.
It involves less-severe symptoms and less likelihood of biological disturbance. It
affects 3–10% of the population, with the incidence increasing with age, and it is
more common in females.
Affective disorders involve a disturbance of mood (cognitive/emotional symptoms)
associated with changes in behaviour, energy, appetite and sleep (biological
symptoms).
Affective disorders can be thought of as pathological extremes of the normal
continuum of human moods, from extreme excitement and elation (mania) to severe
depressive states.
There are two types of affective disorder: unipolar affective disorders and bipolar
affective disorders.
Unipolar affective disorders (about 80% of depressed cases) in which the
mood swings in one direction only (a feeling of depression only)
Bipolar affective disorders (or maniac depressive psychoses, MDP)
characterised by cyclic manifestation of depression followed by mania (20%
of cases)
Monoamine theory of depression
Genetic, environmental and neurochemical influences have all been examined as possible
aetiological factors. The most widely accepted neurochemical explanation of endogenous
depression involves the monoamines (noradrenaline; serotonin (5-HT); dopamine). The
original hypothesis of depression, ‘the monoamine theory’, stated that depression resulted
from a functional deficit of these transmitter amines, whereas conversely mania was caused
by an excess.
The monoamine theory explains why:
Drugs that deplete monoamines are depressant, e.g. reserpine and methyldopa.
A wide range of drugs that increase the functional availability of monoamine
neurotransmitters improve mood in depressed patients, e.g. tricyclic
antidepressants (TCAs) and MAO inhibitors. The concentration of
monoamines and their metabolites is reduced in the cerebrospinal fluid (CSF)
of depressed patients.
, In some post-mortem studies the most consistent finding is an elevation in
cortical 5-HT2 binding.
The monoamine theory cannot explain why:
A number of compounds that increase the functional availability of
monoamines, e.g. amphetamines, cocaine and L-dopa, have no effect on the
mood of depressed patients.
Some older, atypical anti depressants e.g.iprindole, worked without
manipulating monoaminergic systems.
There is a ‘therapeutic delay’ of 2 weeks between the full neurochemical
effects of antidepressants and the start of their therapeutic effect.
It is unlikely, therefore, that monoamine mechanisms alone are responsible for
the symptoms of depression.
Other systems that may be involved in depression include:
The GABA system
The neuropeptide systems, particularly vasopressin and the endogenous opiates
Secondary-messenger systems also appear to have a crucial role in some
treatments.
Unipolar affective disorders
A common unipolar affective disorder is depression, which is characterized by
misery, malaise, despair, guilt, apathy, indecisiveness, low energy and fatigue,
changes in sleeping pattern, loss of appetite and suicidal thoughts.
Attempts have been made to classify types of depression as either ‘reactive’ or
‘endogenous’ in origin. Reactive depression is where there is a clear psychological
cause, e.g. bereavement.
It involves less-severe symptoms and less likelihood of biological disturbance. It
affects 3–10% of the population, with the incidence increasing with age, and it is
more common in females.
