ANTI DEPRESSANTS

definition
a mental state characterized by a pessimistic sense of inadequacy and a despondent lack of activity
a long-term economic state characterized by unemployment and low prices and low levels of trade and investment
natural depression: a sunken or depressed geological formation
sad feelings of gloom and inadequacy
a period during the 1930s when there was a worldwide economic depression and mass unemployment
low: an air mass of lower pressure; often brings precipitation; "a low moved in over night bringing sleet and snow"
depressive disorder: a state of depression and anhedonia so severe as to require clinical intervention
a concavity in a surface produced by pressing; "he left the impression of his fingers in the soft mud"
angular distance below the horizon (especially of a celestial object)
pushing down; "depression of the space bar on the typewriter
emotional symptoms
misery,apathy and pessimism
low self-esteem and pessimism
indecisiveness,loss of motivation
biological symptoms
retardation of thought and action
loss of libido
sleep disturbance and loss appetite
another symptoms
Sad, anxious, or "empty" mood that lasts more than 2 weeks.
Trouble sleeping.
Appetite changes - either less appetite and weight loss, or eating more and weight gain.
Loss of interest in doing things you once enjoyed, including sex.
Feeling restless and cranky.
Nagging physical symptoms that don't get better with treatment (like chronic pain).
Trouble paying attention, making decisions, or remembering.
Feeling tired all the time or like you have no energy.
Feeling guilty, hopeless, or worthless.
Thoughts of suicide or death
the monoamine theory
The monoamine hypothesis of depression predicts an impairment in central monoaminergic function. The lesion may comprise deficiencies in the absolute concentrations of norepinephrine and/or serotonin (5-HT). Depletion studies have shown a correlation between such deficiencies and depressive symptoms. Measurement of the concentrations of the neurotransmitters and their metabolites in cerebrospinal fluid, urine, and plasma of patients with depression has yielded equivocal results regarding the possibility of altered metabolism of these neurotransmitters. Other studies have investigated the possibility of altered numbers and/or affinities of the serotonin and norepinephrine receptors and uptake sites. For example, there is evidence for a reduction in the activity of the serotonin reuptake transporter in patients with depression and an increase in the density of 5-HT2 receptors in the brains of suicide victims. Similarly, in the noradrenergic system, up-regulation of beta-adrenoceptors is consistently observed. Most recently, attention has focused on the possibility that a lesion may occur in the postreceptor, subcellular components of the monoamine systems, such as the second messenger processes. Also, experimental evidence has shown "cross-talk" between the noradrenergic and serotonergic systems. There is therefore substantial clinical and experimental evidence that lesions in the serotonergic and noradrenergic systems are responsible for depression and that antidepressant treatment can reverse these alterations
types of anti depressants
Selective serotonin reuptake inhibitors (SSRIs)
Serotonin-norepinephrine reuptake inhibitors (SNRis)
Noradrenergic and specific serotonergic antidepressants (NaSSAs)
Norepinephrine (noradrenaline) reuptake inhibitors (NRIs)
Norepinephrine-dopamine reuptake inhibitors (NDRIs)
Selective serotonin reuptake enhancers (SSREs)
Melatonergic agonists
Tricyclic antidepressants (TCAs)
Monoamine oxidase inhibitor (MAOIs)
Augmenter drugs
mechanisam of action
Bipolar disorder (BPD), the province of mood stabilizers,
has long been considered a recurrent disorder. For more
than 50 years, lithium, the prototypal mood stabilizer, has
been known to be effective not only in acute mania but
also in the prophylaxis of recurrent episodes of mania and
depression. By contrast, the preponderance of past research
in depression has focused on the major depressive episode
and its acute treatment. It is only relatively recently that
investigators have begun to address the recurrent nature of
unipolar disorder (UPD) and the prophylactic use of longterm
antidepressant treatment. Thus, it is timely that we
address in a single chapter the most promising research relevant
to the pharmacodynamics of both mood stabilizers and
antidepressants.
As we have outlined in Fig. 79.1, it is possible to characterize
both the course and treatment of bipolar and unipolar
disorder in a similar manner. Effective treatments exist for
the acute phases of both disorders; maintaining both types
of patients on such drugs on a long-term basis decreases the
likelihood and intensity of recurrences. Further, because the
drugs are given long-term, they produce a cascade of pharmacologic
effects over time that are ‘‘triggered’’ by their
acute effects. Both classes of psychotropic drugs incur a lag
period for therapeutic onset of action, even in the acute
phase; therefore, studies during the past two decades have
focused on the delayed (subchronic) temporal effects of
these drugs over days and weeks. Consequently, it is widely
thought that the delayed pharmacologic effects of these
drugs are relevant for either the initiation of behavioral improvement
or the progression of improvement beyond that
initiated by acute pharmacologic actions. The early realization
that lithium is effective prophylactically in BPD and
the more recent understanding that antidepressants share
this property in UPD have focused research on long-term
events, such as alterations in gene expression and neuroplasticity,
that may play a significant role in stabilizing the clinical
course of an illness. In our view, behavioral improvement
and stabilization stem from the acute pharmacologic effects
of antidepressants and mood stabilizers; thus, both the acute
and longer-term pharmacologic effects of both classes of
drugs are emphasized in this chapter

MOOD STABILIZERS

The term mood stabilizer within the clinical setting is commonly
used to refer to a class of drugs that treat BPD.
However, for the purpose of our discussion, it is important
to differentiate the three clinical phases of BPD—acute
mania, acute depression, and long-term prophylactic treatment
for recurrent affective episodes. Although a variety of
drugs are used to treat BPD (i.e., lithium, anticonvulsants,
antidepressants, benzodiazepines, neuroleptics), we suggest
that only a drug with properties of prophylaxis should be
referred to as a mood stabilizer and included in this chapter.
Significant evidence supports a therapeutic action for lithium,
both in acute mania and prophylactically in a major
subset of patients with BPD 1. However, the data for longterm
prophylaxis with anticonvulsants (i.e., valproate, carbamazepine),
although supported in part in clinical practice,
remains less well established scientifically
In the absence of a suitable animal model, an experimental
approach, used to ascribe therapeutic relevance to any observed
biochemical finding, is the identification of shared
biochemical targets that are modified by drugs belonging
to the same therapeutic class (e.g., antimanic agents) but
possessing distinct chemical structures (e.g., lithium and
valproate). Although unlikely to act via identical mechanisms,
such common targets may provide important clues