CHE 360 - Depression

clinical symptoms of depression

sad, insomnia, guilt or worthlessness, energy is low, concentration is poor, appetite is down, psychomotor retardation, suicidal

biochemical basis of depression

clinical depression may be due to low levels of the monoamine neurotransmitters norepinephrine (NE), serotonin (also called 5-hydroxytryptamine or 5HT) and dopamine in the mood center of the brain. Sub-optimal levels of serotonin in the brain have also been linked with panic attacks, obsessive-compulsive behavior, migraine headaches, and obesity.

Tricyclic antidepressants (TCA’s)

prevent reuptake of serotonin and norepinephrine (to a lesser degree) at afferent neurons, thus intensifying the effect of serotonin and norepinephrine.

common side-effects of TCA’s

α1 antagonist – orthostatic hypotension

• anticholinergic – dry mouth, tachycardia, blurred vision, photophobia (mydriasis),

urinary retention, constipation

• anti-histamine – sedation, drowsiness

• tachycardia and dysrhythmias, heart block

• increased risk of seizures in epileptics – lowers threshold

• low therapeutic index – dangerous if there is suicide potential – often prescribed in small

amounts

• weight gain

SSRI antidepressants

act by selectively increasing serotonin levels in the portions of the brain controlling mood. Their major advantage over the tricyclic antidepressants is less severe adverse effects. Fluoxetine (Prozac), Paroxetine (Paxil) Sertraline (Zoloft) Citalopram (Celexa) Escitalopram (Lexapro)

common side-effects of SSRI’s

sexual dysfunction(50%)

• nausea (21%)(usually resolves in first week)

• headache (20%)

• agitation, anxiety & hyperactivity (15%)

• insomnia (14%)

• anorexia (11%)

• skin rash (4%)

• suicide risk (rare, but all SSRIs have a black box FDA warning for this).

SARI ANTIDEPRESSANTS (Serotonin Antagonist and Reuptake Inhibitors)

thought to inhibit serotonin reuptake and to block certain serotonin receptors . It is now available as generic trazodone. It is also used as a sedative for insomnia (taken hs) as well as second line antidepressant. Trazodone (Desyrel)

SNRI Antidepressants (Serotonin and Norepinephrine Reuptake Inhibitors)

These are classified separately from tricyclics because they do not have the many adverse effects of TCA’s. Duloxetine(Cymbalta)

NOREPINEPHRINE AND DOPAMINE REUPTAKE INHIBITORS(NDRI’S)

Bupropion (Wellbutrin, Wellbutrin SR(bid) and Wellbutrin XL(qd)) ; Zyban (SR)

Bipolar disorder

characterized by wide fluctuations (over days, weeks or months) between physical and mental hyperactivity (mania) and depression. There are a variety of subtypes of bipolar disorder depending on duration, intensity, and specific nature of the manic and depressed stages

Lithium carbonate

was the drug of choice for treatment of bipolar disorder, although it is losing ground to other drugs because of its poor efficacy in some kinds of bipolar, its numerous adverse effects and its low TI. It works best in euphoric slow cyclers. It is very water soluble and therefore rapidly excreted in urine. It must be taken tid or qid as it is quicly urinated out; sustained release form available

Olanzapine (Zyprexa)

approved for treatment of bipolar disorder in 2000

bupropion (Wellbutrin)

commonly prescribed and is available in generic form. It is a weak inhibitor of NE and dopamine reuptake. There is risk of seizures and cardiac arrhythmias at high dosages. Regular form is taken tid. Like other antidepressants, it takes 3-4 weeks to show effect. Zyban is the same drug for aiding smoking cessation. A sustained release form, Zyban (SR), is available

amitriptyline (Elavil)

tends to be sedating. Taking a TCA h.s. helps induce sleep (remember insomnia is a common problem in depression).

Celexa

is a racemic mixture of mirror image molecules (designated R and S) analogous to left and right handed gloves

Escitalopram

(Lexapro) is the pure S isomer of Celexa and currently has about 60% of the SSRI market in Oregon. It claims fewer side effects due to the absence of the R enantiomer