venlafaxine (Effexor)
Venlafaxine versus stimulant therapy in patients with dual diagnosis ADD and depression.

Hornig-Rohan M, Amsterdam JD.

Depression Research Unit, University Science Center, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

BACKGROUND: Adult attention-deficit disorder (ADD) may either present as chronic depression or be comorbid with major depressive disorder (MDD). The present study examined treatment outcome with antidepressants and/or stimulants in adults with ADD who initially presented with a diagnosis of MDD. METHOD: Seventeen patients with comorbid MDD and ADD were identified: 65% had a history of hyperactivity in childhood, and 41% had a history of treatment nonresponse to two or more antidepressants. Retrospective analysis was performed with patients who received one of three treatments: (i) venlafaxine, bupropion, or tricyclic antidepressant (TCA) monotherapy; (ii) stimulant monotherapy; or (iii) stimulant plus antidepressant therapy. Outcome was based upon change in both MDD and ADD symptoms. RESULTS: Venlafaxine-treated patients (80%) versus patients taking stimulant therapy alone (33%) had at least a moderate reduction in both MDD and ADD symptoms (chi2=2.40, Fisher exact P=.13). Similarly, 88% of patients on stimulants plus antidepressant therapy also showed a reduction in both MDD and ADD symptoms (versus stimulant monotherapy) (chi2 = 7.22, Fisher exact P=.018). There was no difference in response rates between venlafaxine monotherapy and combination stimulant plus antidepressant therapy (chi2=0.13, Fisher exact p=ns). CONCLUSION: Although preliminary in nature, these data suggest that venlafaxine monotherapy may have similar efficacy to a treatment with a combination of stimulant plus antidepressant therapy, and superior to stimulant therapy alone, in patients with comorbid MDD and ADD. Controlled, prospective trials with larger patient samples will be needed to confirm these preliminary observations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11999912&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Venlafaxine in children, adolescents, and young adults with autism spectrum disorders: an open retrospective clinical report.

Hollander E, Kaplan A, Cartwright C, Reichman D.

Department of Psychiatry and the Seaver Autism Research Center, Mount Sinai School of Medicine, New York, New York 10029, USA. e_hollander smtplink.mssm.edu

Autism is characterized by social deficits, communication and language impairments, narrow restricted interests, repetitive behaviors, inattention, and hyperactivity. While selective serotonin reuptake inhibitors have demonstrated efficacy in treating core symptoms of autism, norepinephrine reuptake inhibitors have demonstrated efficacy in symptoms of attention-deficit hyperactivity disorder (ADHD). An open, retrospective clinical study with venlafaxine evaluated its effect on core symptoms of autism as well as associated features of ADHD. Ten consecutive subjects meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for an autism spectrum disorder were treated with venlafaxine, initiated at 12.5 mg per day and adjusted on a flexible basis. Six of 10 completers were judged to be sustained treatment responders, by scoring 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions improvement scale. Venlafaxine was effective in low dosages (mean, 24.37 mg/day; range, 6.25 to 50 mg/day) and was well tolerated. Improvement was noted in repetitive behaviors and restricted interests, social deficits, communication and language function, inattention, and hyperactivity. Controlled treatment trials with venlafaxine are warranted in autism spectrum disorders.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10695900&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Venlafaxine serum levels and CYP2D6 genotype.

Veefkind AH, Haffmans PM, Hoencamp E.

Department of Clinical Chemistry, Zon & Schild Psychiatric Center, Amersfoort, The Netherlands.

Thirty-three patients with depression treated with 225 mg venlafaxine were genotyped for the polymorphic enzyme, debrisoquine 4-hydroxylase (CYP2D6). The relationship between drug and metabolite levels and between genotype and clinical response were investigated. Although the number of responders in this study is insufficient for definite conclusions to be drawn, a target therapeutic concentration ranging from 195-400 microg/L for the sum of venlafaxine and O-desmethylvenlafaxine is suggested. The ratio of O-desmethylvenlafaxine to venlafaxine in the serum concentrations is a measure of metabolic turnover, and can be used to distinguish between ultrarapid and poor metabolizers. All but one of the nonresponders in this study had lower ratios than the responders. Three patients (9%) had homozygous defective CYP2D6 alleles and did not readily metabolize venlafaxine to O-desmethylvenlafaxine, pointing to poor metabolism. In these patients, N-desmethylation was increased. Two out of four patients detected by the ratio as potentially ultrarapid metabolizers were shown to have multiple copies of a functional CYP2D6 gene.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10774634&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Evidence of the dual mechanisms of action of venlafaxine.

Harvey AT, Rudolph RL, Preskorn SH.

Psychiatric Research Institute and the Department of Psychiatry, University of Kansas School of Medicine, Wichita 67214-2878, USA. aharvey kumc.edu

BACKGROUND: Indirect evidence suggests that the antidepressant venlafaxine hydrochloride selectively inhibits serotonin (5-HT) uptake at low doses, whereas at high doses, it inhibits both 5-HT and norepinephrine (NE) uptake. We hypothesized that, in vivo, both high and low doses would inhibit the 5-HT uptake of platelets but that the higher dose would differentially blunt the pressor response to tyramine, a marker for NE uptake. METHODS: Healthy male volunteers aged 18 to 45 years received either 75 mg or 375 mg of venlafaxine hydrochloride per day, the 5-HT uptake inhibitor sertraline hydrochloride (50 mg/d), or the NE uptake inhibitor maprotiline hydrochloride (150 mg/d) (n = 8 for each of 4 treatment groups). Changes in platelet 5-HT uptake and the pressor response to intravenous tyramine were assessed following the initial dose and after 1 and 2 weeks of drug administration. RESULTS: Platelet 5-HT uptake was inhibited by venlafaxine across the dose range and by sertraline but not maprotiline. Inhibition was competitive, related to increases in affinity and not related to capacity. Steady-state drug levels were associated with a 5-HT uptake inhibition of 87% or more in subjects taking venlafaxine or sertraline. The pressor response to tyramine differentially distinguished maprotiline from sertraline and the low dose of venlafaxine but not from the high dose of venlafaxine. CONCLUSION: This study provides the first in vivo evidence in healthy humans that both 5-HT uptake and NE uptake inhibition are mechanisms of action sequentially engaged by venlafaxine over its clinically relevant dose range.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10807491&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine.

Kennedy SH, Eisfeld BS, Dickens SE, Bacchiochi JR, Bagby RM.

Department of Psychiatry, University of Toronto, Centre for Addiction and Mental Health, Ontario, Canada. sidney_kennedy camh.net

BACKGROUND: Recent reports suggest that adverse effects on sexual function occur in up to 50% of patients who are treated with selective serotonin reuptake inhibitor (SSRI) antidepressants. Previously cited low rates were more likely a function of underreporting than underoccurrence. There is less evidence about rates of dysfunction with serotonin-norepinephrine reuptake inhibitor (SNRI) and reversible inhibitor of monoamine oxidase A (RIMA) antidepressants. The purpose of this report is to evaluate disturbances in sexual drive/desire and arousal/orgasm in 107 patients who met criteria for major depressive disorder and received treatment with either moclobemide, paroxetine, sertraline, or venlafaxine. METHOD: All consenting eligible patients who met DSM-IV criteria for major depressive disorder completed the Sexual Functioning Questionnaire, version 1 (SFQ) and were assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D) prior to and after 8 or 14 weeks of antidepressant therapy. Analyses were carried out to examine the effect of gender, drug type, pretreatment level of sexual dysfunction, and drug response on reported sexual dysfunction. RESULTS: Compared with women, men experienced a significantly greater level of drug-related impairment in drive/desire (p < .05), whereas there were no statistically significant differences in levels of arousal/orgasm impairment between men and women. The reported impairment in drive/desire items for men ranged from 38% to 50% and from 26% to 32% for women. No differences were found across the 4 antidepressants in men, whereas in women, rates of dysfunction were generally higher with sertraline and paroxetine, but only significantly so in comparison with moclobemide on some measures (p < .03). Rates of sexual dysfunction with venlafaxine tended to fall between those of SSRIs and the RIMA agent. An unexpected relationship was found between favorable drug response and a decreased level of drug-induced sexual dysfunction. CONCLUSION: Antidepressant-induced sexual dysfunction occurs in approximately 30% to 70% of patients who are treated with sertraline or paroxetine. Lower rates are reported with moclobemide and venlafaxine. Clinicians should evaluate the various aspects of sexual dysfunction before and during antidepressant therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10830148&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR