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_NPJ39iQ&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 D- DSM-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