Chapter 13: Treatments for Depression and Bipolar Disorder
Mental disorder: impairment in normal, behavioural or cognitive functioning.
The DSM requires that an individual experience significant stress from the disorder and that the disorder
does not arise form medical condition with a clear physiological cause.
o For example, the DSM does not qualify Alzheimer’s disease as a mental disorder because
Alzheimer’s diseases derives from clear deterioration from brain tissue.
Major depressive disorder is characterized by at least five depressive symptoms that last 2 weeks or
longer. These symptoms include a depressed mood, lack of interest or pleasure in most activities, change in
body weight, change in sleep patterns, fatigue, feelings of worthlessness, difficulties in thinking or in
concentrating, and recurrent thoughts of death.
Dysthymic disorder (milder version) consists of a depressed mood that occurs nearly everyday for 2
years. In addition, they must have at least two symptoms for depression.
Nonspecific descriptions may be used for some symptoms of depression, such as hunger and sleep. For
example, an individual may sleep most of the day or suffer long bouts of insomnia.
Major depression with psychotic features is characterized by the presence of depression, hallucinations,
and delusions related to depressed mood and negative thoughts.
The Prevalence of Clinical Depression
A potential reason for depression in the elderly may be poor blood flow to the brain.
The term for depressed symptoms associated with poor blood flow in the brain is called vascular
Neuroimaging Techniques and Functioning Differences in Depression
The structural abnormalities in depression involve many structures, including the amygdala, prefrontal
cortex, hippocampus, and nucleus accumbens.
The amygdala appears overactive in depression. Volume reductions are found in the hippocampus in
depression. Under activity in the left dorsal prefrontal cortex. Underactive nucleus accumbens.
o The nucleus accumbens in responsible for reward- and goal-directed behaviour, and the other basal
ganglia structures facilitate movement.
o Although movement is not a feature of depression, approximately half of all Parkinson’s disease
patients report a major depressive episode before the first occurrence of Parkinson’s symptoms.
Antidepressant Drugs and Depression
The first antidepressant drug, iproniazid (Marsilid), was developed for the treatment of TB in 1953.
Classification of antidepressant drugs according to their pharmacological actions and chemical structures,
which has led to the following categories: monoamine oxidase (MAO) inhibitors, tricyclic antidepressant
drugs, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and atypical
The monoamine hypothesis states that a monoamine deficiency causes depressive mood.
Monoamine Oxidase Inhibitors
Researchers have discovered two types of MAO: MAOA and MAOB.
MAOA is found in the brain, peripheral nervous system, and intestinal tract, whereas MAOB is found
mainly in the brain and, to a lesser extent the peripheral nervous system.
In the brain, MAOA resides in dopamine and norepinephrine neurons, and MAOB resides in serotonin and
norepinephrine neurons. Iproniazid became known as the first clinically used antidepressant drug among the MAO inhibitors. They
act by biding to MAO and preventing it from breaking down monoamine neurotransmitters, including
serotonin, dopamine, norepinephrine, as well as tyramine.
Irreversible MAO inhibitors, the drug never releases from MAO. To make up for the loss of MAO
functions, neurons synthesize more MAO.
Reversible MAO inhibitors, the drug temporarily binds to MAO or other compounds such as tyramine to
displace the drug from MAO.
Limitation for the first MAO inhibitors is characterized as the cheese reaction which is a result of an
overactivated sympathetic nervous system leading to increased heart rate, hypertension, sweating, and
inhibited digestion. Doctors advise their patients to rude their consumption of food containing high amounts
of tryamine such as dairy products, meat, and grain products when taking MAO inhibitors.
Modern MAO inhibitors reduce, although do not eliminate, the risk of a cheese reaction.
The first of modern MAO inhibitor, selective MAOB inibitors, such as selegiline primarily inhibit MAOB
enzymes and exhibit weaker binding to MAOA enzymes. This configuration decreases a cheese reaction
risk while enhancing levels for dopamine, norepinephrine and serotonin. Selegiline can be administered as a
skin patch o bypass the intestinal tract where tyramine build-up and a cheese reaction occurs.
The second type of MAO inhibitors, a reversible inhibitor of MAOA (RIMA) selectively inhibit MAOA
but allow for displacement from MAOA by tyramine. By allowing MAOA to break down tyramine,
patients have a lower risk of a cheese reaction.
Tricyclic Antidepressant Drugs
Tricyclic antidepressant drugs block the reuptake of norepinephrine and serotonin and function as
antagonists for various receptors, often including muscarinic acetylcholine receptors.
Shared chemical structures of three connected benzene rings.
Imipramine (first drug in this category) and other tricyclic antidepressant drugs produce certain
pharmacological actions similar to MAO inhibitors.
These drugs do not inhibit MAO, but instead prevent the reuptake of serotonin and norepinephrine in the
neurons that released them. This avoided the cause of cheese reaction which are produced by MAO
Unique adverse effects:
o Their pharmacological actions are less selective than MAO inhibitors. Not only do they block
reuptake of serotonin and norepinephrine but also bind to many receptors throughout the body,
including antagonist actions at muscarinic receptors. Due to this, it can prevent parasympathetic
acetylcholine from binding to these receptors at target sites in the body (dry eyes blurred vision,
constipation, dry mouth, urinary retention). Can also carry risk of cognitive and memory difficulties.
o Many tricyclic antidepressants also block a1 adrenoceptors (norepinephrine receptor), causing
potentially dangerous cardiovascular effects.
o Known to cause weight gain, which could lead to other health concerns such as diabetes II.
Selective Serotonin Reuptake Inhibitors (SSRIs)
Zimelidine was the first selective serotonin reuptake inhibitor.
Selective serotonin reuptake inhibitor (SSRI) blocks serotonin transporters, resulting in greater serotonin
levels within synapses.
Was prescribed to teenagers and children due to the safety of the drug in comparison to MAO inhibitors and
tricyclic drugs. Ultimately, it was found that it resulted in increased suicide risk in children.
Serotonin syndrome, a life-threatening condition characterized by agitation, restlessness, disturbances in
cognitive functioning, and possibly hallucinations. Can be avoided by taking low or moderate doses.
Just as taking SSRIs might lead to serotonin syndrome, abrupt withdrwal may cause a serotonin
Serotonin discontinuation syndrome is characterized by sensory disturbances, disequilibrium, flulike
symptoms, and gastrointestinal effects. Elevations in serotonin levels are likely to cause sexual side effects, including erectile dysfunction, inability
to achieve orgasm, and los of sexual drive.
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
Serotonin-norepinephrine reuptake inhibitors (SNRIs), enhance levels of serotonin and norepinephrine
by blocking serotonin and norepineiphrine transporters.
The push for a new class resulted from the adverse effects of SSRIs, particularly sexual side effects and a
significant population of patients who failed to respond adequately to SSRIs or other antidepressant drugs.
It was found that SNRI always produced a slightly greater improvement compared to an SSRI.
Atypical Antidepressant Drugs
Atypical antidepressant drugs that reduce depression through mechanisms that differ from those of other
The most prescribed is bupropion, which is a reuptake inhibitor for norepinephrine and dopamine and
therefore is unique among the antidepressants for its lack of serotonin elevation.
Limitations in Antidepressant Drug Effectiveness and Development
Length of Response Time
All antidepressant drugs have a lengthy response time. Clinically significant effects occur after 2 weeks of
treatment and generally show full effects after 4 weeks.
The long response time is particularly troublesome for patients with a high risk of suicide.
Treatment-resistant depression is a diagnosis made after successive failed attempts to significantly
reduce depressive sy