Oral three-times-daily bupropion IR was effective and generally well tolerated in the treatment of major depressive disorder (MDD). It was as efficacious and as well tolerated as some tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Moreover, it was associated with less somnolence and weight gain than some TCAs. Twice-daily bupropion SR was also efficacious and generally well tolerated in the treatment of MDD. It was as effective as and had a generally similar tolerability profile to some SSRIs, but had the advantage of less somnolence and sexual dysfunction. The efficacy of bupropion XR in terms of primary efficacy measures was established in two of six well designed placebo-controlled studies. Bupropion XR also demonstrated efficacy in terms of some secondary outcomes in five of these studies. Additionally, bupropion XR was similar, in terms of the primary efficacy outcomes, to the SSRI escitalopram in two placebo-controlled trials and to the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine extended release (XR) in two trials (one of which was placebo-controlled), but not in a third placebo-controlled trial where venlafaxine XR was better than bupropion XR. It was generally as well tolerated as escitalopram and venlafaxine XR, but was associated with less sexual dysfunction than escitalopram. Available clinical data suggest that bupropion is an effective and generally well tolerated option in the treatment of MDD, with the newer formulations having the advantage of reduced frequency of daily administration.

Pharmacological properties of bupropion

As with all antidepressants, the precise mechanism of action of bupropion in MDD is unknown, although bupropion selectively inhibits dopamine and norepinephrine reuptake. The reuptake inhibition potential of bupropion is greater for dopamine than for norepinephrine. Importantly, bupropion does not affect serotonergic pathways and does not act on postsynaptic histamine, alpha- or beta-adrenergic, dopamine or acetylcholine receptors.

Time to reach maximum plasma concentration (Cmax) varied between bupropion formulations (IR ~ 2 h, SR ~ 3 h and XR ~ 5 h). A decreased number of peak plasma levels were associated with bupropion SR and XR, compared with bupropion IR. However, bioequivalent systemic exposure (as assessed by Cmax and area under the plasma concentration-time curve) was established between all formulations of bupropion and its three pharmacologically active metabolites. Steady state is reached within 8 days. Bupropion is extensively metabolized, mainly by cytochrome P450 (CYP) isoenzymes or via carbonyl reduction. As the active metabolites of bupropion reach higher steady-state concentrations than those of bupropion, these metabolites may be of clinical importance. Bupropion has an elimination half-life (t 1/2) of 20–21 hours and is predominantly (87%) excreted in the urine as metabolites. The t 1/2 of the active metabolites of bupropion are ~20, ~33 and ~37 hours. There is potential for drug-drug interactions between bupropion and drugs that affect CYP2B6 and 2D6 metabolism, drugs that are substrates of these isoenzymes and drugs that affect metabolism in general.

Therapeutic efficacy of bupropion

Three-times-daily bupropion IR was effective in the treatment of MDD in a 6-week randomized, double-blind clinical trial in adults with moderate to severe disease, demonstrating greater improvement from baseline in several efficacy measures relative to placebo. Moreover, bupropion IR was as effective as the SSRI fluoxetine, the TCAs nortriptyline, amitriptyline and doxepin, and the atypical antidepressant trazodone in reducing symptoms of depression and anxiety assessed by several efficacy measures in 6- to 13-week trials in adults with MDD.

Similarly, twice-daily bupropion SR was effective in the treatment of MDD in 8-week, randomized, double-blind clinical trials in adults with moderate to severe disease, demonstrating greater improvements from baseline in several efficacy measures relative to placebo. In addition, bupropion SR was effective in preventing relapse in one 52-week relapse-prevention study in a similar patient population. In comparative trials, there were no significant differences between bupropion SR and the SSRIs sertraline or fluoxetine in adults and the SSRI paroxetine in elderly patients with moderate to severe disease in randomized studies of 6- to 16-weeks’ duration. Furthermore, bupropion SR was as effective as the SSRI sertraline and the SNRI venlafaxine XR with respect to remission rates (primary efficacy measure) in patients who were switched from citalopram therapy because of a lack of remission of symptoms or because they could not tolerate citalopram in the large, randomized, multicentre STAR*D trial. In the same study, bupropion SR was shown to be as effective as the serotonin receptor agonist buspirone, in terms of remission rates, when used to augment citalopram therapy in a similar patient population. There were some benefits with bupropion SR relative to buspirone therapy as demonstrated by a greater reduction from baseline in self-rated 16-item Quick Inventory of Depressive Symptomology (QIDS-SR-16) score and a lower QIDS-SR-16 score with bupropion compared with buspirone therapy at study end.

Two of six placebo-controlled trials in adult and elderly patients with moderate to severe MDD demonstrated greater improvements from baseline in the 30-item self-rated Inventory of Depressive Symptomology scale or Montgomery-Asberg Depression Rating Scale (MADRS) total scores (primary efficacy measures) with once-daily bupropion XR relative to placebo. However, in the trial involving elderly patients, although significant reduction from baseline in MADRS total scores in bupropion XR relative to placebo recipients in the last-observation-carried-forward (LOCF) analysis (primary efficacy measure) was not observed, significant improvements from baseline were observed in the protocol-defined observed-case or per-protocol analyses and according to the rank analysis of covariance and robust regression analysis. Benefit with respect to some secondary measures was observed with bupropion XR relative to placebo in five of six placebo-controlled efficacy studies in adults and the elderly.

There were no significant differences between bupropion XR and the SSRI escitalopram in terms of the change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score (primary efficacy measure) in patients with moderate to severe disease in placebo-controlled studies of 8 weeks’ duration. Similarly, in two 8- and 12-week studies, one of which was placebo-controlled, in patients with similar disease, there were no significant differences between bupropion XR and the SNRI venlafaxine in terms of primary (MADRS total score) or secondary (HAM-D-17 total score) efficacy measures. Additionally, in the 12-week study, more patients achieved remission with bupropion XR than venlafaxine XR therapy. However, in one 8-week placebo-controlled study, venlafaxine XR was better than bupropion XR in terms of MADRS total scores (primary efficacy measure).

Tolerability of bupropion

All three formulations of bupropion (IR, SR or XR) were generally well tolerated in patients with moderate to severe MDD. Adverse event-related withdrawal rates in pooled analyses were 5–11% in bupropion IR, SR or XR recipients. Overall, the most common treatment-emergent adverse events reported in bupropion IR, SR or XR versus placebo recipients were headache (20–26% vs 20–23%), dry mouth (16–28% vs 7–18%) and nausea (13–23% vs 8–19%); agitation was another common treatment-emergent adverse event reported in 32% of bupropion IR compared with 22% of placebo recipients. Bupropion SR and XR were also well tolerated in terms of their effects on sexual functioning in patients with MDD.

Most adverse events associated with bupropion SR or XR relative to placebo were mild to moderate in severity. However, there is a dose-dependent risk of seizures (0.4% with bupropion IR 300–450 mg/day; 0.1% with bupropion SR 100–300 mg/day, increasing to 0.4% with bupropion SR 400 mg/day; and 0.1% with bupropion XR ?450 mg/day) associated with the use of bupropion. Although the effect of bupropion (IR, SR or XR) on suicidality is not clear, it is recommen ded that patients should be monitored closely. In general, the effects of bupropion (IR, SR or XR) on vital signs (systolic and diastolic blood pressure and heart rate) were small, although some changes (largely an increase in ?12% of patients) in these parameters with bupropion XR were of potential concern or were sustained (in 3–11% of patients) during therapy.

Although the tolerability profile of bupropion (IR, SR or XR) was generally similar to that of TCAs (nortriptyline, amitriptyline and doxepin), an atypical antidepressant (trazodone), SSRIs (including sertraline, fluoxetine and escitalopram) and an SNRI (venlafaxine XR) in patients with moderate to severe MDD, some adverse events were reported in fewer bupropion than comparator recipients.

Bupropion SR and XR were associated with less sexual dysfunction than SSRIs, such as sertraline and escitalopram. Bupropion XR had a more favourable effect on sexual function than venlafaxine XR in one study, which assessed the parameter as the primary outcome measure, but not in two others where sexual function was assessed as a secondary outcome measure. Bupropion IR and SR were associated with less somnolence relative to some TCAs and SSRIs. On the other hand, the incidence of dry mouth was higher with bupropion IR and SR than with some SSRIs, but lower than that observed with some TCAs. In patients receiving citalopram therapy augmented with bupropion SR or buspirone in the STAR*D trial, discontinuation rates due to intolerance were lower with bupropion SR plus citalopram than with buspirone plus citalopram.

Although bupropion IR, SR and XR were associated with a weight gain of >2.3 kg (>5 lb), the incidence of weight gain was ~4-fold lower with bupropion IR than with TCAs. Bupropion (IR, SR or XR) was also associated with a weight loss of >2.3 kg (>5 lb). However, the incidence of weight loss with bupropion IR was approximately twice that observed with TCAs. No clinically significant changes in weight were observed in bupropion SR or placebo recipients after 52 weeks of therapy.

Zopiclone is known colloquially as a “Z-drug”. Other Z-drugs include zaleplon (Sonata) and zolpidem (Ambien and AmbienCR) and were initially thought to be less addictive and/or habit-forming than benzodiazepines. However, this appraisal has shifted somewhat in the last few years as cases of addiction and habituation have been presented. It is recommended that zopiclone be taken on an “as needed” basis. Daily or continuous use of the drug is not usually advised. While it acts on the same benzodiazepine receptors as the benzodiazepine family of drugs it is not classed as a benzodiazepine (with which it shares a number of characteristics and effects) due to its differing molecular structure. Zopiclone is classed as a cyclopyrrolone derivative. [Wikipedia.org]

Since 1987 when zopiclone was introduced into clinical practice, extensive evaluations have shown that some rebound changes can be detected in healthy individuals. In patients with insomnia more than 20 studies have assessed rebound. Rebound can be found in such patients, but is usuallymore frequent and present in greater intensity in comparison groups given triazolam.

Studies in the elderly have been carefully reviewed by Soldatos and his colleagues. Some deterioration in the soundness of sleep has been detected but the amount of rebound insomnia following zopiclone discontinuation is relatively weak. Although one would certainly expect rebound in a hypnotic with a half-life of around 5 h, the frequency and severity of such rebound seems definitely less than those observed with comparative benzodiazepines such as triazolam and temazepam.

Longer-term studies have been designed to detect withdrawal as well as rebound phenomena. A large scale study in France recorded any reactions to stopping zopiclone after it had been taken for up to 12 months. Over a thousand patients took part, most of whom stopped abruptly. In only 1.3% of the overall population was there substantial evidence of any withdrawal. The symptoms comprised anxiety, irritability, malaise and perceptual changes, which are characteristic of a sedativetype withdrawal reaction. Two parallel studies evaluated the withdrawal following long-term zopiclone (somnosan, ximovan) and long-term zolpidem. Thirty eight percent of those who withdrew from zopiclone had apparent symptoms, but these were also found in 27% of those who continued. Most of the withdrawal symptoms related to sleep complaints. Excluding these, no treatment-emergent increase in withdrawal symptoms was found.

An evaluation has beenmade of the utility of zopiclone substitution in facilitating the withdrawal of flunitrazepam. Twenty-four volunteers with insomnia and a history of long-termbenzodiazepine hypnotic usewere assessedwith both subjective and objective measures during a 5-week substitution with zopiclone and subsequent withdrawal or continuation on flunitrazepam. Withdrawal from flunitrazepam was accompanied aworsening of sleep quality, both subjectively and objectively. No such deterioration was seen in the zopiclone - substituted groups.

Lemoine and Ohayon completed a much larger scale study. Over 1000 patients being treated with a hypnotic were allocated to one of three treatments: gradual substitutionwith zopiclone; immediate substitutionwith zopiclone (somnosan, ximovan); remained on their benzodiazepine. The gradual and abrupt substitution group had improved sleep during this initial phase; the abrupt substitution group did best. During withdrawal, the last group (benzodiazepine-using) fared worst and more resumed their medication. The PSG withdrawal effects of zopiclone (7.5 mg), zolpidem (10 mg) and triazolam (0.25 mg) as compared with placebo were studied in 38 healthy subjects over 4 weeks. Slight, non-significant rebound effects on sleep continuity were detected after withdrawal of zopiclone and zolpidem. Total sleep time and sleep efficiency were lower the first night after cessation of triazolam.

A very detailed review of zopiclone noted its proven efficacy and good tolerability.With respect to withdrawal, clinical trials showed no evidence for significant rebound insomnia. The risk of withdrawal reactions was very low, although dependency and abuse have been reported.

Post-marketing surveillance and pharmacovigilance data contain few convincing cases of withdrawal from zopiclone. Most consist of rebound insomnia, but there are a few instances of withdrawal convulsions following high-dose dependence. A reviewof 25 zopiclone discontinuation studies found rebound effects andwithdrawal symptoms to be minimal.

via www.anxietyonlinepharmacy.com

Thanks to the “Prozac (fluoxetine) revolution” of the 1980s and 1990s, a majority of people in America know someone who has used antidepressants. Over 34 million people in the United States have been issued prescriptions for Prozac (fluoxetine) or another selective serotonin reuptake inhibitor (SSRI). In other words, one American in ten has used

antidepressants and studies have estimated that one in six people will have a major depressive episode in their lives (Figure 1.2).

The term “depressive” does not just signify a simple feeling of sadness, but can also refer to any mental disorder with symptoms of moodiness and melancholy — anxiety or eating disorders, for example. Depression is no longer a disease that is shameful or that must be kept hidden. Depression is also no longer as debilitating as it was in the early twentieth century, before the development of antidepressant drugs. Still, the costs of depression to society in terms of lost work, treatment, and other associated expenses have been estimated to be in excess of $30 billion per year. Even with all the progress in antidepressant research, there is an even bigger push to find more antidepressants that work faster and better since rates of depression appear to be growing every year.

But how can a chemical change a person’s outlook on life? If the root of depression is caused by a problem in a person’s life, is it right to take a pill rather than confront the problem? Or is depression something organic, a brain imbalance that can only be cured by taking antidepressants? Are antidepressants, in essence, changing a person’s personality? Furthermore, how well do they work (all hype aside)?

Antidepressants became a media obsession in the early 1990s largely following the publication of Prozac Nation, Elizabeth Wurtzel’s memoir of adolescent depression and its unexpected “cure” by a new kind of antidepressant called fluoxetine, better known as Prozac. Listening to Prozac (fluoxetine), psychiatrist Peter Kramer’s best-selling book, continued the drug’s run of publicity with its descriptions

of formerly depressed patients becoming social, focused, and successful professionals. But on the trail of Listening to Prozac’s success are many other books, which protest that Prozac (fluoxetine) and other antidepressants from the same family (selective serotonin reuptake inhibitors) do not deserve the reputation that the media has given them. Furthermore, other researchers have published findings that refute the effectiveness of selective serotonin reuptake inhibitors (SSRIs) as compared to older antidepressants, straight talk therapy, or even herbal mood-boosters such as St. John’s wort. One study even claims that SSRIs are no better than placebo (the sugar pill used as a control in clinical studies) and might, in fact, be making patients worse.

via: www.anxietyonlinepharmacy.com

1. Don’t try to get anything past us. Prescriptions for painkillers or sleeping aids always get extra scrutiny.

2. We’re not serving fries in here. I’d think twice about using a drive-through pharmacy. Working there distracts us-not a good thing when it comes to pharmaceuticals.

3. We’re human… and we make mistakes (about two million a year). Ask if we use a bar-code system to help keep us from pulling the wrong drug off the shelf or giving the wrong strength of the right drug.

4. Sometimes we can’t read the doctor’s handwriting either. E-prescribing can help, but as of 2006, fewer than 20 percent of prescriptions were being electronically transmitted.

5. I hate your insurance company as much as you do. “Even if something’s working for you, the insurance company may insist you switch to something else,” says pharmacy owner Stuart Feldman.”I’m stuck in the middle trying to explain this to customers.”

6. We can give flu shots in most states.

7. A less-qualified pharmacy technician may have actually filled your prescription. Currently, there is no national standard for their training and responsibilities.

8. Generics are a close match for most brand names. But I’d be careful with blood thinners and thyroid drugs, since small differences can have big effects.

9. I can give you a generic refill that’s different from the one you started with. When in doubt, ask. Online resources like cvs.com let you double-check your pill.

10. We’re not mind readers, and there’s not some big computer database that tracks your drugs and flags interactions for pharmacists everywhere. Use one pharmacy. If you start using a new one, make sure we know what you’re taking.

11. Avoid the lines. It gets busy Monday and Tuesday evenings, since many new prescriptions and refills come in after the weekend.

12. Look into the $4 generics offered by chains like Target, Kroger, and Wal-Mart. And it can’t hurt to ask your pharmacy if it will match the price.

13. Yelling at me won’t help. If I can’t reach your doctor and/or insurance company to approve a refill, there’s nothing I can do about it. “It’s frustrating,” says pharmacist Daniel Zlott, “but I’d be breaking the law in some states if I gave it to you.”

Source:

• Dr. Daniel Zlott, oncology pharmacist, National Institutes of Health; Cindy Coffey, PharmD; Greg Collins, pharmacy supervisor, CVS/pharmacy, California; Stuart Feldman, owner, Cross River Pharmacy, New York

via www.rd.com

1. Don’t put up with the silent treatment. Pharmacists are required by law in most states to counsel patients and answer their questions. If your pharmacist seems too busy to do talk with you, take your business someplace else.

2. An over-the-counter version might do the trick. You may just need to take more pills and forgo insurance reimbursement. But always talk to your pharmacist, and do the math.

3. Ask about over-the-counter drugs. “People assume that if it’s over-the-counter, it’s safe,” says Daniel Zlott, a pharmacist at the National Institutes of Health. “I’ve seen serious complications.”

4. Go ahead and call me doctor (I’m just not that kind of doctor). Since mid-2004, pharmacy students must pursue a doctorate in pharmacy (Pharm.D) in order to be licensed. Pharmacists licensed before then must have at least a Bachelor of Pharmacy and pass a series of exams. Either way, your pharmacist has spent more time studying drugs than even your doctor has.

5. Open up a little. “The better I know you as a patient—your health history, your family, and how busy your life is—the better I can tailor medications to fit your lifestyle,” says Zlott. “You may not want to take a drug three times a day, for example, and I’ll know that if I know you.”

6. “People take too many drugs, definitely,” says Stuart Feldman. Two out of every three patients who visit a doctor leave with at least one prescription for medication, according to the Institute for Safe Medication Practices. “Drugs are an easy solution,” says Feldman, “but there are other solutions.”

7. Talk to me—and check my work. Half the prescriptions taken in the U.S. each year are used improperly, and 96 percent of patients nationwide don’t ask questions about how to use their medications. When you pick up your prescription, at a minimum, ask, What is this drug? What does it do? Why am I taking it? What are possible side effects? and How should I take it? Not only does this help you to use the drug correctly; it’s also a good way to double-check that you’re getting the right drug.

8. We’ll save you money if we can. “A good part of a pharmacist’s time is spent dealing with patients and their incomes,” says pharmacist Cindy Coffey. Part of that is suggesting generic or OTC alternatives. Or if a doctor has prescribed a newer drug with no generic alternative available, says Zlott, “I might call the doctor to suggest an older drug that’s equally effective.”

9. “Some pharmacies are so volume-driven that the pharmacist can’t look up all day,” says pharmacist Cindy Coffey. There were a record 3.8 billion prescriptions filled in the U.S. in 2007—a 13 percent increase from 2003.

via www.rd.com

The fundamental question is, Why is natural (herbal) medicine a necessity for good health? A 2007 report gave some insight into this question. It disclosed that Americans have a shorter life expectancy than people in 41 other countries. This is eye opening, considering that we in the United States on average spend more on health care than people anywhere else. What’s behind this discouraging statistic? There are various possibilities, including the fact that almost 70 percent of U.S. adults are now overweight, with 32 percent of these considered obese.  Lack of medical insurance is another likely reason. A third reason, which you won’t read about in the press, is the suppression of nutritional and holistic therapies in mainstream U.S. health care. Approximately 80 percent of the world’s population rely on plants and other holistic medicines as a primary form of medicine. For people in many cultures, medicine begins in the backyard,where family gardens yield plentiful fruits, vegetables, and healing herbs; and natural, nontoxic therapies such as massage and nutritional therapy are widely used.We encourage you to incorporate holistic healing into your health care—and to urge your insurance carrier to cover these therapies.

Can you have confidence in the dietary and supplement approaches recommended in this book? You certainly can. We have cited key studies and scientific references validating their effectiveness. In addition, among this book’s three authors, we have well over a combined 75 years of clinical experience. It is one thing to read a study on the effectiveness of a particular natural (herbal) medicine, it is another to monitor a patient and see a health transformation take place.

There is a lot more science behind natural and nutritional therapies than most people, including medical doctors, are aware of. Thousands of scientific studies from around the world are published monthly validating the effectiveness and safety of natural (herbal) medicine.

Natural (herbal) medicine is a diverse system of medicine that offers a variety of healing therapies.While there are different philosophies and styles of natural therapies, they have common principles. The following six principles are embraced by modern-day naturopathic and holistic doctors.

1. First, do no harm. Whenever possible, use therapies that have the lowest risk of causing adverse effects. In general, nutritional and other natural approaches are quite safe.
2. Use the healing power of nature. Our bodies have an inherent healing mechanism.We can aid that healing mechanism through the use of nutritional and various natural (as well as conventional) therapies. From a divinely complex design, we see how the medicinal properties of foods, herbs, and other natural substances nourish and stimulate the healing ability of the body.
3. Find the cause. The best way to help individuals with their health needs  is to treat their root causes. Holistic doctors are generally very effective at identifying and treating the root cause of an illness.When possible,we should strive to remove the underlying cause of an illness rather than just eliminate or suppress its symptoms.
4. Treat the whole person.Wellness or illness comes from a complex interaction of physical, emotional, dietary, genetic, environmental, lifestyle, and other factors. One is best helped by taking all these factors into account. This includes the physical, mental, emotional, and spiritual aspects of a person.
5. Practice preventive medicine. Illness is often caused by diet, habits, poor stress-coping mechanisms, environmental pollutants, and lifestyle. Good holistic doctors assess risk factors and susceptibility to disease and make appropriate recommendations to prevent illness, or to keep a minor illness from developing into a more serious or chronic disease. The emphasis is on building health rather than on treating symptoms.
6. Practice the principle of doctor as teacher. The original meaning of the word “doctor” is teacher. A good doctor will educate patients on what they should do to achieve health as opposed to just relying on medical intervention.

Reference:

• Ohlemacher, Stephen. 2007. U.S. life expectancy lags behind 41 nations. USA Today, August 11, Health and Behavior section.

TABLE 1: Oral Contraceptives Containing Low Doses of Estrogen

Ethinyl estradiol 20 mg/Levonorgestrel 0.1 mg (AlesseTM)
Ethinyl estradiol 20, 10 mg/Desogestrel 0.15 mg (MircetteTM)
Ethinyl estradiol 20, 30, 35 mg/norethindrone 1.0 mg (Estrostepw)
Ethinyl estradiol 20 mg/norethindrone acetate 1.0 mg (Lo-Estrinw 1/20)
Ethinyl estradiol 20 mg/drospirenone 3.0 mg (YazTM)

Many oral contraceptives have been studied in the treatment of acne (Table2 ). These include those containing ethinyl estradiol in combination with cyproterone acetate (Diane, Dianette), ethynodiol diacetate (Demulen), levonorgestrel (TriPhasil, Alesse), norgestimate (Ortho Tri-Cyclenw), desogesterel (Desogen), and drosperinone (Yasmin, Yaz). Numerous studies point to the efficacy of ethinyl estradiol/cyproterone acetate oral contraceptives (Diane and Dianette) in the treatment of acne. Reductions in inflammatory lesion count on the order of 50% to 75% have been reported. Two large studies involving a total of approximately 500 women with moderate acne were conducted with ethinyl estradiol 35 mg/norgestimate (Ortho Tri-Cyclen). Improvement in inflammatory lesions, total lesions, and global assessment was noted with this oral contraceptive after six months of treatment (46,47). There was a 50% to 60% improvement in inflammatory lesions. Decreases in serum free testosterone and an increase in sex hormone-binding globulin were noted in the active group. Two large, six-month, placebo-controlled trials (350 and 371 women, respectively) were conducted

TABLE 2 Oral Contraceptives Studied in Acne

Demulen (ethinyl estradiol 35 mg/ethynodiol diacetate)
Diane, Dianette (ethinyl estradiol 50, 35 mg/cyproterone acetate)
Estrostep (ethinyl estradiol 20, 25, 30 mg/norethindrone)
Alesse (ethinyl estradiol 20 mg/levonorgestrel)
Ortho Tri-Cyclen (ethinyl estradiol 35 mg/norgestimate)
Desogen (ethinyl estradiol 30 mg/desogestrel)
Yasmin (ethinyl estradiol 30 mg/drospirenone)
Yaz (ethinyl estradiol 20 mg/drospirenone)
Triphasil (ethinyl estradiol 30 mg, 40 mg/levonorgestrel)

using ethinyl estradiol 20 mg/levonorgestrel (Alesse) in the treatment of acne. In each study, the oral contraceptive demonstrated significantly greater reduction in acne lesion counts and improvement in global assessment scores compared with placebo. The reduction in inflammatory lesion count was on the order of 47%. A study of 128 women with mild-to-moderate acne compared the efficacy of ethinyl estradiol 30 mg/drospirenone (Yasmin) and ethinyl estradiol 35 mg/cyproterone acetate (Diane-35) in the treatment of acne for nine cycles (50). Both treatments produced comparable reductions in acne lesion counts, with an approximate 60% reduction in inflammatory lesion count. Both treatments also reduced sebum production and yielded comparable increases in sex hormone-binding globulin. Two large placebo-controlled studies involving a total of approximately 593 women with moderate acne, found improvement in inflammatory lesions, total lesions, global assessment, and quality of life in women who were treated for six months with a triphasic oral contraceptive that contains doses of 20 to 35 mg of ethinyl estradiol in combination with 1.0 mg norethindrone acetate (Estrostep). In these studies, inflammatory lesion counts were reduced by approximately 47% .

Oral contraceptives that have been approved for the treatment of acne in the United States include ethinyl estradiol 35 mg/norgestimate (Ortho Tri-Cyclen) ethinyl estradiol 20 to 35 mg/norethindrone acetate (Estrostep), and ethinyl estradiol 20 mg/drospirenone (Yaz).

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Definition of Alprazolam (Xanax, Xanor, Tafil)

Alprazolam is a tranquilizer. It belongs to a group of drugs called benzodiazepines. In the United States alprazolam is sold under brand name Xanax.

Purpose of Alprazolam (Xanax, Xanor, Tafil)

The United States Food and Drug Administration has approved alprazolam to treat anxiety, panic disorder, and anxiety associated with depression. Occasionally alprazolam is used to treat alcohol withdrawal, but it is not FDA-approved for this use, and is not normally the first drug tried in treating alcohol withdrawal symptoms.

Description of Alprazolam (Xanax, Xanor, Tafil)

Alprazolam is classified as a benzodiazepine. Benzodiazepines are sedative-hypnotic drugs that help to relieve nervousness, tension, and other anxiety symptoms by slowing the central nervous system. To do this, they block the effects of a specific chemical involved in the transmission of nerve impulses in the brain, decreasing the excitement level of the nerve cells.

All benzodiazepines cause sedation, including drowsiness and reduced mental alertness. However, one benefit of alprazolam is that it causes somewhat less drowsiness than many other benzodiazepine drugs.

Alprazolam comes in 0.25-mg, 0.5-mg, 1-mg and 2-mg tablets, and 1-mg/ml solution.

KEY TERMS

Benzodiazepines—A group of central nervous system depressants used to relieve anxiety or to induce sleep.

Glaucoma—A group of eye diseases characterized by increased pressure within the eye significant enough to damage eye tissue and structures. If untreated, glaucoma results in blindness.

Recommended dosage of Alprazolam (Xanax, Xanor, Tafil)

The recommended initial adult dose for anxiety is 0.25–0.5 milligrams (mg) taken three times daily. This dosage may be increased every three to four days to a maximum total of 4 mg daily. Dosage for alcohol withdrawal usually totals from 2–2.5 mg daily given in several small doses throughout the day.

The starting dose for treating panic disorder is 0.5 mg three times daily. This dosage may be increased every three to four days until the total daily dosage ranges from 2–10 mg. The total amount should be divided in at least three even daily doses. Average doses for anxiety associated with depression range from 2.5–3 mg daily divided into even doses.

Precautions of Alprazolam (Xanax, Xanor, Tafil)

Alprazolam should not be used by patients who are pregnant, have narrow angle glaucoma, take ketoconazole or itraconazole, or those who are allergic to this or any other benzodiazepine drug. The dose of alprazolam must be carefully regulated and individualized in the elderly (over age 60), people with liver or kidney disease, and those taking other medications used to treat mental disorders.

Because alprazolam is a nervous system and respiratory depressant, it should not be taken with other similar depressants, such as alcohol, other sedatives, sleeping pills, or tranquilizers. People taking this drug should not drive, operate dangerous machinery, or engage in hazardous activities that require mental alertness at least until they see how the drug affects them.

Alprazolam should be used under close physician supervision in patients with history of substance abuse. Like other benzodiazepines, alprazolam can be habit-forming. Risk and severity of dependence appears greater in patients taking doses larger than 4 mg daily. However, smaller doses may cause dependence if alprazolam is taken longer than 12 weeks.

Suddenly discontinuing alprazolam after several weeks may cause uncomfortable symptoms of withdrawal. Withdrawal symptoms in people who have taken alprazolam three months or longer may include seizures, anxiety, nervousness, and headache. Patients should discuss with their doctor how to gradually discontinue alprazolam use to avoid such symptoms.

Side effects of Alprazolam (Xanax, Xanor, Tafil)

The most common side effects of alprazolam include sedation, dizziness, drowsiness, insomnia, and nervousness. The intensity of these side effects usually declines gradually and subsides in about eight weeks. A drop in blood pressure and an increase in heart rate may also occur in people who are taking alprazolam.

Decreased sex drive, menstrual disorders, and both weight gain and weight loss has been associated with alprazolam use. People who experience the side effects of stomach upset, nausea, vomiting, and dry mouth should eat frequent, small meals and/or chew sugarless gum. Alprazolam has been associated with both diarrhea and constipation, as well as tremor, muscle cramps, vision disturbances, and rash.

Interactions of Alprazolam (Xanax, Xanor, Tafil)

Alprazolam interacts with a long list of other medications. Anyone starting this drug should review the other medications they are taking with their physician and pharmacist for possible interactions. The most severe interactions occur with antifungal medications, such as ketoconazole, itraconazole, and fluconazole. These are associated with alprazolam toxicity (excessive sedation, fatigue, slurred speech, slowed reactions and other types of psychomotor impairment).

Estrogens (female hormones), erythromycin (an antibiotic), fluoxetine (Prozac, Sarafem), cimetidine (Tagamet), isoniazid, and disulfiram (Antabuse) can increase the effects of alprazolam. Carbamazepine can make alprazolam less effective. When alprazolam is combined with other sedative drugs (tranquilizers, sleeping pills) or alcohol, its depressants effects are more intense. These combinations should be avoided.

Resources

1. Kay, Jerald. Psychiatry: Behavioral Science and Clinical Essentials. Philadelphia: W. B. Saunders Company, 2000.
2. Lacy, Charles F. Drug Information Handbook. Hudson, OH: Lexi-Comp, Inc. 2002.
3. Pharmacia and Upjohn Company Staff. Product Information: Xanax, alprazolam. Kalamazoo, MI: Pharmacia and Upjohn Company, 1999. Ajna Hamidovic, Pharm.D.

Some of the potential partners were “of a similar profile to Unilever” but interim chief operating officer, Keith Thomson, said the company was “open to exploring collaborative structures” with European and international partners.

“One of the good things to come out of the Unilever situation is that we have greater flexibility to deal with the ingredient,” Thomson told NutraIngredients.com.

“It was a setback when they decided not to proceed with the ingredient, and they have their reasons for that, but we are very positive about its future.”

In a statement, Phytopharm said it would be putting more resources behind its pharma operations that include the neural ingredients Cogane and Myogane as part of a “major review of business strategy”.

This restructuring meant reducing staff levels from 40 to 25 and implementing “a cost saving programme” that would reduce the company’s overall expenditure by 20 per cent.

It said its management team was “devoting considerable effort to generating such funding from specific charities, grant funding as well as other viable sources.”

Unilever leaving

But in regard to its functional food operations, Phytopharm in a statement admitted it had been a difficult four months following the collapse of the partnership with Unilever.

That separation saw then chief executive officer, Daryl Rees, and chief financial officer, Piers Morgan, resign over an undisclosed dispute about the terms of the dissolution, and Thomson and CEO Sandy Morrison took up interim positions. The company is searching for a new CEO.

“Our functional food programme was negatively impacted by the Unilever decision not to proceed with the Hoodia extract programme,” Phytopharm said.

“The Company is still firmly committed to the potential benefits of Hoodia extract as a functional food targeting weight management and is in early stage discussions with a number of interested alternative partners. It is Phytopharm’s intention to find a partner or licence the Hoodia programme if a satisfactory business proposition emerges.”

But in the meantime it would “limit expenditure on this programme”.

Upon pulling out of the partnership in November, Unilever global media relations director, Trevor Gorin said: “Data suggests using the extract would not meet our safety and efficacy standards. We have entered talks with Phytopharm to end the partnership.”

But Gorin would not reveal the safety and efficacy grounds on which the ingredient failed Unilever, nor why such information was not available before Unilever and Phytopharm signed the deal in December, 2004.

When asked if Unilever was of the opinion hoodia did not work as a weight-loss ingredient, Gorin said, “not in Unilever-branded products”.

Hoodia gordonii is a small cactus that grows in the Kalahari desert and is believed to act as a “satiety stimulator”. Phytopharm gained a global license to market it in 1997.

Its flesh has been eaten by the San people of the Kalahari desert for centuries to suppress appetite and research has isolated a molecule within the plant, given the name P 57, that appears to possess appetite suppression properties.

via www.nutraingredients.com