And a One, and a Two… Exercise for Depression
As an adjunct to medication and psychotherapy or by itself, exercise can be an effective treatment for depression.
Milnacipran (Savella) is the third compound to be approved in the United States for the treatment of fibromyalgia syndrome.
Preventing Depression in Adolescents
Current depression in parents negates the positive effects of a group cognitive behavioral prevention program in preventing depression in adolescents.
Anticholinergic Medicines and Cognitive Decline in the Elderly
Anticholinergic medications can impair cognition and memory, especially in elderly patients.
Predictors of Mortality in Depressed Patients following Cardiac Events; Disruption of Dopamine Neurotransmission in ADHD
Raising the SSRI Dose: Does It Help?
Selective serotonin reuptake inhibitors (SSRIs) do not appear to have an obvious relationship of dose to likelihood of benefit.
Generic Antidepressants: Bioequivalent?
Generic formulations of antidepressants may not have the same pharmacokinetics and clinical effects as the original brand-name versions.
Lamotrigine in Borderline Personality Disorder
Preliminary research found lamotrigine (Lamictal) superior to placebo in improving symptoms of affective instability and impulsivity in patients with borderline personality disorder.
Generic Antidepressants: Bioequivalent?
When patent protection expires for a medication, generic "equivalent" products become available. An obvious benefit is that they are less costly—both to insurers and consumers. The U.S. Food and Drug Administration standards require that the 90% confidence interval of the generic/reference (original brand name compound) ratio for the area under the concentration-time curve and the maximum plasma concentration fall within the 80% to 125% range. Thus, a generic compound is considered "bioequivalent" to the original medication if levels in healthy volunteers' bodies range up to 25% higher or 20% lower than those achieved by the patented compound.
In real life, clinicians sometimes observe that patients switched from brand name to generic medicines show symptomatic worsening or even recurrent episodes of their psychiatric or medical conditions. Occasionally, side effects appear to increase. But scientific data on such issues are hard to come by. There are few systematic studies comparing the pharmacokinetics and clinical effects of generic and brand name pharmaceutical products. Therefore, a recent small pharmacokinetic study is interesting.
Chenu and coworkers in Canada and Austria compared the pharmacokinetics of the generic and brand name formulations of two antidepressants—venlafaxine (Effexor and others) and citalopram (Celexa and others).1 Twelve healthy volunteers took the extended release form of venlafaxine, 75 mg, and citalopram, 40 mg, in a randomized, crossover design. Each subject received the generic and brand name form of each antidepressant in a randomized order.
Plasma levels of citalopram were similar after the generic product and Celexa were ingested. However, levels of venlafaxine and its active metabolite were much higher after the generic product compared with Effexor. The maximum plasma concentration (Cmax) was 50% higher following generic venlafaxine. The active metabolite O-desmethylvenlafaxine was also higher—between 43% and 48% more with the generic product than with Effexor between 3 and 6 hours after dosing. There were no differences in steady state between generic venlafaxine and Effexor at day 5. Consistent with the elevated plasma concentrations, subjects reported three times more side effects with the generic than with the brand name medicine. The authors conclude that the generic formulation of extended-release venlafaxine released its active ingredient more rapidly and outside the prescribed norm.
This small study comparing generic and brand name versions of two antidepressants must be generalized with great caution. Nevertheless, it supports clinical observations that when patients take different products of the same active ingredient, they may experience clinically meaningful changes. It would be prudent, therefore, to advise patients to be aware of changing products—which can occur when pharmacies shift their purchasing contracts, as well as when a specific medication goes "off patent." A change in preparation can diminish efficacy or increase side effects.
1Chenu F, Batten L, Zernig G, Ladstaetter E, Hebert C, Blier P: Two generic antidepressant medications and their bioequivalence or bio-inequivalence. Paper presented at the 49th annual meeting of the New Clinical Drug Evaluation Unit, Hollywood, FL, June 29 – July 2, 2009.