Lecture 8: Antidepressants and Mood Stabilizers– 8th November 2016
Overview:
Depression and mania: Clinical aspects.
Monoamine theories of depression
First antidepressant drugs
Tricyclic antidepressants
MAO inhibitors (monoamine oxidaze inhibitors)
SSRIs: Selective serotonin reuptake inhibitors
SNRIs & SNARIs: These also affect noradrenaline
Mood stabilizers: Lithium and Antiepileptic drugs
ECT: Electroconvulsive shock. Magnetic stimulation
Overview and comparison with behavioural/cognitive therapies
Depression and Mani: Clinical aspects
Mood state fluctuation is ‘normal’ - to a moderate extent.
Depression: Characterised by periods of very low moods: feel worthless,
low interest/pleasure, disturbed sleep, lacking drive or energy, thoughts of
death/suicide.
Mania: Hyperactivity, euphoria, flights of fancy, multiple task initiation,
talkative, grandiosity, financial extravagance. Mania is like the opposite to
depression, always looking for more things to do. Mania is also
characterised by conceptual extravagance.
, Manic-depression (bipolar mood disorder): Alternating high and low
moods. Sometimes in rare instances very regular cycles…low for 18 hours…
normal for 6 ..high for 12….normal for 12…This allows for predictable
periods with great accuracy. Manic-depression (bipolar) is much more rare
than unipolar depression.
Depression - Most distressing for the individual affected.
Mania - The most destructive psychiatric disorder for
family/employer/friends/bank manager. A person with mania is not
distressed but they are very socially disruptive.
Lewinsohn et al. (1995): Purpose of the study was to examine prevalence,
clinical characteristics, and mental health treatment services utilization of
adolescents with bipolar disorders and manic symptoms. The lifetime
prevalence of bipolar disorders was approximately 1%. An additional 5.7%
of the sample reported having experienced a distinct period of abnormally
and persistently elevated, expansive, or irritable mood even though they
never met criteria for bipolar disorder (“core positive” subjects). The rate of
manic symptoms in these subjects was similar to that reported in clinical
samples, and the course of bipolar disorder was relatively chronic.
Compared with adolescents with a history of major depression and a
“never mentally ill” group, the bipolar and core positive subjects both
exhibited significant functional impairment and high rates of comorbidity
(particularly with anxiety and disruptive behavior disorders), suicide
attempts, and mental health services utilization. These data highlight the
clinical and public health significance of even the milder and subthreshold
cases of bipolar disorder in adolescence.
, Monoamine theories: Noradrenaline (NA) and Serotonin (5-
hydroxytryptamine or 5-HT)
Schildkraut (1965): First person to talk about this. Depression associated
with a relative deficit in NA, while mania reflects a functional excess of NA.
Luchins (1976): Later serotonin was added by Luchins. Deficits in 5-HT
proposed as an additional core neurotransmitter.
These emerging models reflected novel developments in knowledge about
drug actions, rather than clinical data (the findings for evidence for the
models are based on the effects of different drugs, antidepressants, and
not clinical data). Simple basic models…useful for developing and testing
ideas. These are the two main models for depression.
Some people may have low levels of one but not the other or low levels of
both.
Monoamine Theory: Its Evolution and Development
Three main forms of drug evidence during its evolution and development:
1. Reserpine (Indian snakeroot or Rauwolfia): Depletes monoaminergic
presynaptic storage vesicles (depletes all amine stores). Less
neurotransmitter available for release following an action potential… hence
low moods and depression. Significant side-effect in a minority of those
treated for schizophrenia (see earlier lecture), or for hypotension. It is used
for depletion of dopamine to help with schizophrenia but because it also
leads to depletion of serotonin and others, a side effect is depression and
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