I would recommend... trying desipramine or nortriptyline first, as like reboxetine, they potently inhibit the reuptake of NE. They also have an excellent track record spanning at least 30 years. I have not been impressed with what I have seen with reboxetine. I tried it. Real bad experience, but that's only me. I would not eliminate it from consideration, however. If you haven't investigated the tricyclics yet, I would recommend trying one of them first. I don't think there is any real advantage to reboxetine with respect to side effects.
Tardive dyskinesia.... is caused by chronic blockade of dopamine receptors, as antipsychotic drugs do. This is the exact opposite of what is being discussed here, which is blockading dopamine reuptake, resulting in increasing dopamine transmission and consequent stimulation of those dopamine receptors. Your hand tremor is likely the result of stimulating serotonin 2A receptors from Prozac's blockade of serotonin reuptake.
Efficacy of sertraline in severe generalized social anxiety disorder: results of a double-blind, placebo-controlled study. (Liebowitz MR, DeMartinis NA, Weihs K, Londborg PD, Smith WT, Chung H, Fayyad R, Clary CM.
New York State Psychiatric Institute, New York, NY, USA. leibowitz@nyspi.cpmc.columbia.edu)
BACKGROUND: Generalized social anxiety disorder is an early onset, highly chronic, frequently disabling disorder with a lifetime prevalence of approximately 13%. The goal of the current study was to evaluate the efficacy and tolerability of sertraline for the treatment of severe generalized social anxiety disorder in adults. METHOD: After a 1-week single-blind placebo lead-in period, patients with DSM-IV generalized social phobia were randomly assigned to 12 weeks of double-blind treatment with flexible doses of sertraline (50-200 mg/day) or placebo. Primary efficacy outcomes were the mean change in the Liebowitz Social Anxiety Scale (LSAS) total score and the responder rate for the Clinical Global Impressions-Improvement scale (CGI-I), defined as a CGI-I score RESULTS: 211 patients were randomly assigned to sertraline (intent-to-treat [ITT] sample, 205), and 204 patients, to placebo (ITT sample, 196). At week 12, sertraline produced a significantly greater reduction in LSAS total score compared with placebo (mean last-observation-carried-forward [LOCF] change from baseline: -31.0 vs. -21.7; p =.001) and a greater proportion of responders (CGI-I score CONCLUSION: The results of the current study confirm the efficacy of sertraline in the treatment of severe social anxiety disorder.
Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with 11C McN 5652.
(((Kent JM, Coplan JD, Lombardo I, Hwang DR, Huang Y, Mawlawi O, Van Heertum RL, Slifstein M, Abi-Dargham A, Gorman JM, Laruelle M.
New York State Psychiatry Institute, New York, NY 10032, USA. JMK14@columbia.edu)))
RATIONALE: Although selective serotonin reuptake inhibitors (SSRIs) are widely used in the treatment of anxiety and depressive disorders, the occupancy of the serotonin reuptake transporter (SERT) achieved in humans at typical clinical doses by these agents remains poorly characterized. OBJECTIVE: The purpose of this study was to determine the occupancy of the SERT achieved in vivo by the SSRI paroxetine in social phobia patients at typical antianxiety doses. METHODS: Measures of SERT availability were obtained with positron emission tomography and the SERT radiotracer [(11)C](+)-McN 5652 in five patients with social phobia before and during treatment with paroxetine at usual therapeutic doses (20-40 mg per day). RESULTS: Occupancy of the SERT by paroxetine was high in all subjects and in all regions measured after 3-6 months of continuous treatment. CONCLUSIONS: The results of this study in an anxiety disorder sample are consistent with previously reported results in a depressed sample and suggest that paroxetine at therapeutic doses achieves very high occupancy levels of the SERT
Efficacy of citalopram and moclobemide in patients with social phobia: some preliminary findings.
((((Atmaca M, Kuloglu M, Tezcan E, Unal A.
Firat (Euphrates) University, School of Medicine, Department of Psychiatry, 23119 Elazig, Turkey. matmaca_p@yahoo.com))))
The efficacy of irreversible and reversible monoamine oxidase inhibitors (MAOIs) in the treatment of social phobia (SP) is well established. Recently, selective serotonin reuptake inhibitors (SSRIs) have been used more frequently. In the present study, the efficacy and side-effect profile of citalopram, an SSRI, and moclobemide, the only MAOI used in Turkey, were compared. The 71 patients diagnosed with SP according to DSM-III-R were randomly assigned to two subgroups; citalopram (n = 36) or moclobemide (n = 35). The study was an 8-week, randomized, open-label, rater-blinded, parallel-group trial. All patients were assessed by Hamilton anxiety rating (HAM-A), Liebowitz social anxiety (LSAS), clinical global impression-severity of illness (CGI-SI) and clinical global impression-improvement (CGI-I) scales. There was a similar percentage of responders (citalopram 75%, n = 27 and moclobemide 74.3%, n = 26), with a >50% or greater reduction in LSAS total score and ratings of "very much" or "much improved" on the CGI-I. None of the patients withdrew fromthe study.
The results of the present study suggest that citalopram has shown promising results in patients with SP. Copyright 2002 John Wiley & Sons, Ltd.
Spotlight on paroxetine in psychiatric disorders in adults.
((((Wagstaff AJ, Cheer SM, Matheson AJ, Ormrod D, Goa KL.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz))))
Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or = 60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.
Depression, antidepressants, and sexual function. Victor BS.California Pacific Medical Center, AIDS Clinical Trials Unit Subsite, San Francisco, CA.
Recent studies have suggested that serotonin reuptake inhibitors (SSRI's), prescribed for the relief of depression, can cause sexual dysfunction in up to fifty percent of those taking them. The SSRI's--including fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil)--affect mood stabilization by promoting the transmission of the neurotransmitter serotonin, although enhancing serotonergic function can decrease libido or lead to erectile difficulties. As an alternative to lowering antidepressant dosages and risking losing therapeutic gains, administering serotonin-blockers, such as cyproheptadine (Periactin) and yohimbine (Yocon), has been shown to restore sexual function. However, the serotonin antagonist, cyproheptadine, causes sedation and can reverse the antidepressant or anti-obsessive effect of the SSRI. Yohimbine enhances transmission of the neurotransmitter epinephrine, increasing the flow of blood to erectile tissue and stimulating sexual desire by activating the cerebral cortex. Its drawbacks are increased levels of panic attacks and higher required dosages. Other potential biochemical stratagems are: amantadine (Symmetrel), bromcriptine (Parlodel), and buspirone (Buspar), which enhance dopamine and serotonin transmission; and bethanecol (Urechline), which enhances choline transmission. One study indicates improved sexual response when the nonserotonergic, mildly dopamine-enhancing buproprion (Welbutrin) is substituted for fluoxetine.
Choosing the Right SSRIs for Social Phobia
In May 1999, paroxetine became the first medication to be approved by the Food and Drug Administration as a treatment for social phobia.
Although selective serotonin reuptake inhibitors (SSRIs) are a standard first-line treatment among prescribing physicians, paroxetine is not at the top of the list. Nor, for that matter, is any single agent sufficient in many cases.
"The greatest amount of available data at this point is with paroxetine, but it's likely all SSRIs are similarly effective," said Dr. Mark Pollack, director of the anxiety disorders treatment and research program at Massachusetts General Hospital, Boston. "We don't have data, such as head-to-head trials, that say one [SSRI] is better than another for social phobia."
Dr. Bruce Lydiard, director of the mood and anxiety program at the Medical University of South Carolina, Charleston, said he tailors the drug to the patient. For patients who have sleep problems, paroxetine is a likely option; if lethargy is an issue, a more activating agent such as sertraline or citalopram may be more appropriate.
Although Dr. Lydiard uses fluoxetine, he is likely to opt for an agent with a shorter half-life if the patient has had no prior experience with SSRIs.
In addition to their apparent efficacy in social phobia itself, SSRIs have a broad spectrum to recommend them, Dr. Lydiard said. "You see a fair amount of comorbid major depression, posttraumatic stress disorder, or panic in these patients."
"Start low, go high" seems to be a common plan. Although intolerance to stimulation and other SSRI side effects is less pronounced than when the drugs are used for panic disorder, some patients may be exquisitely sensitive to bodily sensations or "quite hypochondriacal" and require a slow escalation of the dose, Dr. Lydiard said. He said he often begins with one-fourth the dose he'd use for depression (for example, 5 mg of fluoxetine or 12.5 mg of sertraline), but may end 1½ times higher, he said.
"I'm pretty cautious," agreed Dr. Franklin R. Schneier, associate director of the anxiety disorders clinic at New York State Psychiatric Institute in New York, who says he typically initiates social phobia treatment with half the usual starting dose for depression (for example, 10 mg of paroxetine), reaching the antidepressant level in 3-4 weeks. "At that point, if I'm not seeing any benefit or side effects, I might go up some more.
"For most people with social phobia, the situation is very chronic. They've had it for 5-10 years and are not in an immediate crisis, so there's no pressure to push the dose and make a quick decision. You have the luxury of a reasonably full trial."
But this may require some patience. "It may take weeks or months to get a full, comprehensive reduction in distress," Dr. Pollack said. "It takes a while [for the patient] to trust the anxiolytic effects of the medication and to expose himself to difficult situations."
Although there are not much data defining the length of an adequate trial, Dr. Pollack will consider a substantial dose increase if there has been no progress after 4 weeks, and then augmentation if not much has happened 2-3 weeks after that.
In the long run, augmentation often is necessary. "The target is getting the patient as close to well as possible. We want to push patients until they're pretty comfortable in social situations and able to do whatever they want to," he said. At least half will not achieve this goal with SSRIs alone.
Most often, this means an anxiolytic. "Sixty percent of the people I treat get some benzodiazepines," Dr. Lydiard said. "Sometimes just knowing it's in his pocket keeps the patient from panicking."
Among the benzodiazepines, clonazepam is a typical first choice. Dr. Pollack said that he may add the drug at the outset of treatment—before the SSRI—or use it to cover stimulant effects of the SSRI in a patient who is unusually sensitive. Buspirone is an alternative when a benzodiazepine is contraindicated. A more recent option is gabapentin. "My experience with this drug has been quite positive. ... It's a useful addition," he said.
Dr. Lydiard noted that he may use bupropion to augment an SSRI if improvement is inadequate or to manage sexual side effects.
Switching rather than augmentation has its place, particularly if the response to the first drug is negligible. Dr. Lydiard is likely to go to another SSRI, while Dr. Schneier will more often chose a different class altogether, either clonazepam (if comorbid depression or dependence is not an issue) or an MAO inhibitor, particularly phenelzine. That will depend on how amenable the patient is to following a diet and how trustworthy the person is. "I wouldn't be comfortable [giving an MAO inhibitor] if a patient is too impulsive or has a history of noncompliance," he said.
The efficacy of drugs shouldn't obscure the role of cognitive-behavioral therapy (CBT) in the role of social phobia. Dr. Schneier, who is trained in this modality, said he often recommends it as a first-line approach for someone who has not had it before. Those patients for whom he prescribes medication will also be getting some CBT, "in a formal or informal way," perhaps through his encouraging exposure to difficult situations.
In Dr. Schneier's experience, the response to CBT is less dramatic than to medication, but it tends to be longer lasting. And when an SSRI alone is inadequate, the addition of CBT may make adjunctive medication unnecessary, he said.
Zoloft Gets FDA OK
For Social Phobia - Pfizer
NEW YORK (Reuters) - Pfizer Inc. on Monday said it had won permission from US regulators to market its blockbuster depression drug Zoloft for additional use as a treatment for "social anxiety disorder."
People with the condition, also known as social phobia, often fear public speaking, acting in plays, playing musical instruments in public and eating in front of others, according to the Merck Manual of medical information--situations that in an earlier era might have been characterized as shyness.
The New York-based company said Zoloft is the first member in its popular class of depression drugs, known as selective serotonin reuptake inhibitors (SSRIs), to win approval for long-term treatment of patients with the anxiety disorder. It was also approved for acute, or short-term, treatment for the disorder.
Pfizer said people with the disorder experience "anxiety, fear and avoidance behaviors" in certain social situations.
Analysts have said its approved use for social-phobia could help sustain or boost sales of Zoloft, which boasted fourth-quarter global revenues of $775 million. Pfizer said Zoloft is the most-prescribed SSRI in the United States. Other members of the class include GlaxoSmithKline's Paxil and Eli Lilly's Prozac.
venlafaxin för social fobi....
BARCELONA, SPAIN -- October 11, 2002
-- Pooled data from two studies indicates that the serotonin-noradrenaline reuptake inhibitor (SNRI) venlafaxine XR has significantly better anxiolytic activity than placebo in the short-term treatment of generalised social anxiety disorder (SAD).
This finding was reported here at the 15th Congress of the European College of Neuropsychopharmacology (ECNP).
Venlafaxine significantly reduced the overall symptoms of generalised SAD as well as fear and avoidance factors in social and performance settings, noted lead investigator Richard Mangano, PhD, clinical researcher at Wyeth Research in Collegeville, Pennsylvania. At 12 weeks, he added, 47 percent of the subjects responded to venlafaxine XR compared to 32 percent receiving placebo.
The investigators pooled data from two multicentre, double blind, placebo-controlled, parallel-group studies of outpatients with generalised SAD.
The researchers used the Liebowitz Social Anxiety Scale (LSAS) to calculate primary efficacy indications from the pooled data. They also used the subscales of the LSAS -- including performance, social interaction, avoidance factors, and some fear factors (public speaking) -- as well as the fear, avoidance, and physiologic factors of the Social Phobia Inventory (SPIN).
Both studies employed a placebo lead-in phase of seven plus-or-minus three days, followed by a 12-week, randomised, flexible-dose study of venlafaxine XR 75-225 mg/day (259 subjects) or placebo (273 subjects). Each study ended with a 14-day optional tapering-off period.
The analysis indicated that venlafaxine XR performed significantly better than placebo during weeks 3 to 12, based on LSAS total adjusted mean scores.
Mean baseline LSAS for venlafaxine XR and placebo was 88.9. Mean placebo LSAS at week three was 76.8, and mean LSAS for venlafaxine XR was 72.6 (p=0.007 for weeks one to three). Mean placebo LSAS at week 12 was 68.1, and mean LSAS for venlafaxine XR was 57.2 (pPrevious research has connected the serotonin and noradrenaline neurotransmitters to symptoms of SAD. However, prior to this study, SAD therapy research has been limited solely to antidepressants that selectively inhibit the reuptake of serotonin (SSRIs).
"This finding may lead to expanded options for the treatment of this disorder," reported Dr. Mangano.
The study was supported by funding from Wyeth Research.
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