Depression
A Pathopharmacological Approach
Depression is a serious medical disorder characterized by
sadness and despondent behavior.
It isn’t something you can just snap out of.
Pathophysiology
Because of the complexity of both psychosocial and
neurobiological aspects of depression, it is difficult to
determine an exact cause of this mental disorder.
• Monoamine hypothesis of depression suggests
that there is a deficit of certain neurotransmitters in the
brain which is responsible for corresponding
characteristics of depression.
• Serotonin is responsible for such behaviors as anxiety,
anger, appetite, sexuality, sleep, and mood.
• Norepinephrine is responsible for alertness, energy,
anxiety, attention, and interest in life.
• Dopamine is responsible for attention, motivation,
pleasure, reward, and interest in life.
Risk Factors
• Studies show an influence of genetic factors in depression to
be about 30-40%.
• Non-genetic factors, which account for the remaining 60-70%
are due to unfavorable childhood events and recent traumatic
personal events; examples are the death of a loved one and
divorce. Other psychosocial causes include having a poor
social network and major life changing events.
Forms of Depression
• Situational depression evolves from life circumstances that
cause stress, such as major life changes, death, empty nest
syndrome, and job loss.
• Dysthymic disorder symptoms are those of major depression
except they are less severe. A patient complains of not feeling
well or being able to function normally.
• Postpartum Depression affects up to 80% of new mothers.
About 10% will develop major depression.
• Seasonal affective disorder (SAD) is due to decreased daylight
hours, which result in increased melatonin release.
• Psychotic depression is typified by intense mood swings, loss
of contact with reality, delusions, and hallucinations.
Clinical Manifestations of depression
•
Depressed mood and apathy towards things that used to bring pleasure
•
Feeling sad or unhappy most of the day
•
Irritability caused by insignificant incidences
•
Difficulty in concentrating and decision making
•
Lack of energy and constant fatigue
•
Feelings of worthlessness and guilt
•
Unexplained crying episodes
•
Thoughts of suicide and death
Diagnostic Tests
• Major depression is characterized by a depressed
mood for more than two weeks and at least 5 of
the symptoms of depression. This is
accompanied by an inability to manage everyday
tasks.
• Care must be taken to rule out medical and
neurological disorders that can mimic the clinical
symptoms of depression such as side effects from
certain drugs and disease states like thyroid
gland disorders and early Alzheimer’s disease.
Pharmacotherapy for the treatment of
depression
• Antidepressants are categorized by their mechanism of
action. They include:
• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin and norepinephrine reuptake Inhibitors
(SNRIs)
• Norepinephrine and dopamine reuptake inhibitors
(NDRIs)
• Tricyclic antidepressants
• Monoamine oxidase inhibitors (MAOIs)
• SSRIs selectively block the reuptake of serotonin in the
presynaptic nerve terminals which increases the level in the synaptic
space. This increases the amount of serotonin available for
neurotransmission.
• Examples include: citalopram, escitalopram oxalate, fluoxetine,
sertraline and fluoxetine.
• SNRIs selectively block the reuptake of both serotonin and
norepinephrine. The increase availability of these neurotransmitters
causes mood elevation.
• Examples include: duloxetine and venlafaxine
• Adverse effects of both these categories include: nausea, dry
mouth, insomnia, headache, GI disturbances and sexual
dysfunction. Suicidal ideations should be closely monitored
when initiating treatment.
• NDRIs block the action of the norepinephrine transporter and the
dopamine transporter. This causes an increase of extracellular
concentration of both and leads to increased neurotransmission.
•
•
Example: Bupropion
Side effects include: headache, nausea, dry mouth, insomnia, mild itching and sweating.
• Tricyclic Antidepressants inhibit the reuptake of both norepinephrine
and serotonin thereby increasing their availability for neurotransmission.
•
•
Examples: Amitriptyline, imipramine, doxepin, nortriptyline
Side effects include: drowsiness, dizziness, orthostatic hypotension, dry mouth, blurred
vision, and sexual dysfunction. Suicidal ideations should be closely monitored with
initiation of treatment.
• MAOIs limit the breakdown of norepinephrine, serotonin, and dopamine
leading to an increase amount available for neurotransmission.
•
•
Examples: isocarboxazid, phenelzine, selegiline, tranylcypomine
Side effects: drowsiness, dizziness, orthostatic hypotension, blurred vision, nausea and
sexual dysfunction. Suicidal ideations should be closely monitored with initiation of
treatment.
• Evidence based treatment modalities for depression include:
• Psychotherapy, counseling, cognitive behavioral therapy and
phototherapy.
• Alternative treatments include: acupuncture and repetitive cranial
magnetic stimulation
• Severe cases unresponsive to pharmacotherapy may require
electroconvulsive therapy.
YouTube Video
• http://www.youtube.com/watch?v=NWY_NPJ
39iQ&feature=em-share_video_user
• This video does an excellent job summarizing symptoms, treatments and
research associated with depression. Hearing from a patient who has
recovered from depression gives a poignant reminder of the struggle
involved with the disease.
• References:
•
Hasler, G. (2010). Pathophysiology of depression: Do we have any solid
evidence of interests to clinicians? World Psychiatry, 9(3), 155-161.
Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/
PMC2950973/
• USA, National Center for Biotechnology Information. (2000). Appendix DDSM-IV-TR Mood Disorders. Retrieved from
http://www.ncbi.nlm.nih.gov/books/NBK64063/
•
Adams, M., Holland, L. N., & Urban, C. Q. (2014). Pharmacology for
nurses: A pathophysiologic approach (4th ed.). Upper Saddle River,
NJ: Pearson.
• Delgado, P. L. (2000). Depression: The case for a monoamine deficiency.
Journal of Clinical Psychiatry, 61(6), 5-12. Retrieved from http://
www.ncbi.nlm.nih.gov/pubmed/10775018