Dr James Schaller
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Celexa and Lexapro
vs. Regular SSRI's

A Continuing Education Lecture for Doctors

In my research I have found that anti-depressants are not all the same and some have problems rarely mentioned to you.

DRUG POLYPHARMACOLOGY
IN MAJOR DEPRESSSION

30-45% of those treated for Major Depression are incompletely treated by their medication. While Lithium and Thyroid (T3) augmentation is suggested as having the most data for helping these patients, leading research psychopharmacologists often add anti-depressants to anti-depressants first.

New approaches to the treatment of refractory depression (J Clinical Psychiatry 2000;61:26)

LINEAR AND NONLINEAR BLOOD LEVELS

I believe non-linear kinetics offer surprise increases with parallel rapid increased interactions. Specifically, serum levels and liver drug presentation can increase strikingly and non-linearly, causing side effects and sudden interactions.

Sertraline and citalopram have linear pharmacokinetics

Paroxetine and fluoxetine/norfluoxetine have nonlinear pharmacokinetics

Pharmacokinetics of selective serotonin reuptake inhibitors (Pharmacol Therapy 2000;85:11)

OBESITY AND GLUCOSE TOLERANCE

PURE SEROTONIN AGENTS vs. NOREPINEPHRINE (NE)

Many psychiatric medicines increase weight.

In the past, patients hated the weight gain, but physicians were just happy they were stable.

A female waist of 34 1/2 inches or a male waist of 40 inches (tape measure only) increases diabetes risk thousands of percent and all major causes of death.

One review raises concern that Norepinephrine (NE) reuptake inhibition produces increased synaptic catechols and poorer glucose control:

*increasing serum glucose

*reducing insulin sensitivity

Applies to Nortriptyline, Strattera? Effexor? Duloxetine?

Paroxetine's Well Documented Weight Gain

*Studies lasting only 12 weeks, with skinny elderly and using a TCA (nortriptyline) as the "control" say the patients got back to "normal baseline." Silly.

*In a 26-32 week trial of paroxetine, sertraline and fluoxetine, all had some weight increase but paroxetine had both "significant" weight gain and the very highest weight gain.

(Fluoxetine versus sertraline and paroxetine in major depression disorder: changes in weight with long-term treatment. J Clinical Psychiatry 2000;61:863-7)

Paroxetine use over 2 years associated with "a substantial increase" in breast cancer.

The odds ratio is 7.2 (American J of Epidemiology 2000;151:951-7)

I propose that since breast cancer is highly correlated with metabolites from fat estrogen (E1 or estrone) metabolites, 16 OH-E1 and 4 OH-E1, that perhaps weight gain is the mechanism.

Duloxetine

Dual agent with high serotonin and neurepinephrine mechanisms.

Beneficial if no 2D6 Interactions

More Interactions than Sertraline

Will compete with Venlafexine (Effexor)


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