Introduction

Manic depression, also called bipolar disorder, afflicts some 4 million Americans. Characterized by severe mood swings between incredible elation and deep depression, the disorder has been difficult to treat. Many patients either do not respond to drug therapy or stop taking their medication because of unwanted side effects.

Now a new drug has entered the arena: Zyprexa (olanzapine), manufactured by Eli Lilly. Zyprexa had already been approved for the treatment of schizophrenia, and recently got the green light from the FDA for use in patients with manic depression.

Clinical Study Results

Studies evaluating the effectiveness of the drug in patients with acute mania showed that those who took Zyprexa (olanzapine) achieved a significantly greater improvement in their symptoms than patients who received a placebo. Other studies have shown that Zyprexa is as effective as lithium, another agent commonly used to treat manic depression.

What You Should Know

Like other drugs in its class, Zyprexa does have side effects, including dry mouth and weight gain. Drowsiness and dizziness have also been associated with Zyprexa, so patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that they will not experience these effects. Because there are other potential side effects, patients with manic depression who are interested in Zyprexa (olanzapine) should consult their physicians.

Zyprexa

Introduction

Bipolar disorder is a lifelong psychiatric disorder that features mood swings between mania and depression, and afflicts some 4 million Americans. Although lithium, valproate, carbamazepine, and antipsychotics have been prescribed to treat the disorder, many patients do not respond to these treatments or stop taking them due to unwanted side effects. Now there is another drug available for these patients: Eli Lilly received FDA approval to market Zyprexa (olanzapine) – a drug originally approved for schizophrenia – for the treatment of manic depression.

How It Works

Zyprexa is an antipsychotic drug. Although the exact mechanism of action is unknown, it is proposed that the drug’s activity is mediated through a combination of dopamine and serotonin type 2 (5-HT2) antagonism, as well as antagonism at other receptors with similar affinities.

Zyprexa (olanzapine): Clinical Study Results

A randomized, double-blind, placebo-controlled study was conducted over a 3-week period in patients with acute mania. Clinical response was compared between 70 patients who received 10 mg Zyprexa once daily and 69 patients who received placebo. After the first day of treatment, the Zyprexa dose was adjusted upward or downward, as clinically indicated, by one capsule, within the permitted range of one to four capsules. Clinical response was defined as a decrease of 50% or more in the Young Mania Rating Scale total score, from baseline to endpoint. At the end of the study period, significantly more patients taking Zyprexa (48.6%) showed clinical improvement than those taking placebo (24.2%). Although somnolence, dry mouth, dizziness and weight gain occurred more often with Zyprexa than with placebo, no patients discontinued treatment due to these side effects.

What the Patient Should Know

As with other antipsychotic drugs, Zyprexa (olanzapine) is associated with several side effects. Since orthostatic hypotension has been reported with Zyprexa, patients who experience this effect should be advised to avoid standing up too quickly. Because somnolence and dizziness have been associated with Zyprexa, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that they will not experience these effects. Patients should not breast-feed during Zyprexa treatment and should inform their physicians if they become pregnant while on the treatment. They should also avoid alcohol and tell their physicians if they are taking other medications, since Zyprexa may interact with other drugs (for example, it may potentiate the effect of antihypertensive drugs and antagonize those of levodopa and dopamine agonists). Since Zyprexa may elevate transaminase levels, it should be used with caution in patients with hepatic impairment. Patients with a history of seizures should tell their physicians, since Zyprexa may increase the risk of seizures. Other side effects associated with Zyprexa (olanzapine) include restlessness, constipation, dry mouth, and weight gain.

* note: social anxiety disorder is characterized by the fear of being observed or evaluated by others; sufferers report an overwhelming fear of embarrassment in social and performance situations.
* researchers at the University of Southampton conducted a 12-week, multi-centre, double-blind, placebo-controlled clinical trial to compare the efficacy of Paxil (20-50 mg daily) to placebo, in 290 patients with social anxiety disorder.
* found a statistically significant symptom improvement in patients treated with Paxil within as little as four weeks of treatment onset, as measured by the Liebowitz Social Anxiety Scale (LSAS), which provides an assessment of a patient’s level of fear and avoidance of performance and/or social situations.
* the researchers say that Paxil was associated with a definitive reduction in symptoms of social anxiety disorder, increased participation in social activity, as well as a significant improvement in overall well being.
* Paxil (paroxetine), from SmithKline Beecham Pharma Canada, has been approved in 82 countries for the treatment of depression, obsessive-compulsive disorder and panic disorder in patients over the age of 18 and is indicated for the treatment of generalized social anxiety disorder in 35 countries, including the U.S.

* Researchers at Scott & White Memorial Hospital in Temple, Texas, randomized 57 women diagnosed with moderate-to-severe premenstrual syndrome (PMS) to treatment with Zoloft or a placebo at 14 days prior to the expected onset of menses to collect data; participants were switched to the other therapy after two months.

* Found that Zoloft-treated women showed significant improvement in PMS-related symptoms, compared to placebo recipients, and that while most women improved in their first cyle of Zoloft therapy, the benefits were greater after the second cycle of treatment.

* There were no serious side effects among Zoloft users, but about 10% of women complained of insomnia.

* Researchers say that since Zoloft is eliminated from the body in about 26 hours it is suitable for short-term use. – authors note that further study is needed to confirm the findings and to assess the long-term effects of Zoloft therapy in women with premenstrual syndrome (PMS).

* Researchers at Detroit’s Wayne State University randomized 168 patients with panic disorder to receive either sertraline or a placebo for 10 weeks to collect data.

* Found that the average number of panic attacks suffered weekly by patients treated with sertraline dropped 88%, compared to a 53% drop seen in placebo recipients. – authors further note that patients treated with sertraline showed significant improvements in measures of quality of life enjoyment and on personal assessments of the severity of their illness.

* The report notes that sertraline treatment was not associated with “jitteriness,” which is a common side-effect of older antidepressants used to treat panic disorder.

Vestra: Introduction

As a selective norepinephrine reuptake inhibitor (SNRI), Vestra is the first of a new class of antidepressant drugs. This new mechanism of action appears to produce fewer side effects, such as nausea, headache, and sexual dysfunction, compared with traditional antidepressants. Vestra also possesses a faster onset of action compared to selective serotonin reuptake inhibitors (SSRI), tricyclics, and monoamine oxidase inhibitors, commonly used to treat depression.

Vestra: How It Works

A lack of norepinephrine in the central nervous system (CNS) of depressed individuals is hypothesized to be responsible for several specific symptoms of depression, such as lack of energy, interest, and motivation. Vestra inhibits the reuptake of norepinephrine by the presynaptic nerve terminals. As a result, the neurotransmitter remains in the synapse for a longer period of time.

Vestra: Clinical Study Results

Several clinical studies were conducted to determine the safety, efficacy, and tolerability of Vestra. One study involved 283 patients with recurrent DSM-III-R major depression. These patients were randomized to receive either Vestra or placebo for 46 weeks in a double-blind phase. Vestra was associated with a significantly lower relapse rate than placebo (22% vs. 56%; p < 0.001), as well as a greater cumulative probability of maintained response (p = 0.0001) during long-term treatment. The proportion of relapse- free patients who remained in the study was significantly higher in the Vestra group than in the placebo group at the end of the first six months (61% vs. 40%) and the second six months (88% vs. 59%) of treatment.

A double-blind, randomized, parallel-group, multicenter trial, including 168 patients with acute major depressive episodes, was conducted to compare Vestra to fluoxetine, an SSRI. The patients were administered either Vestra 8-10 mg/day or oral fluoxetine 20-40 mg/day for 8 weeks. Both treatments were found to be similarly effective as assessed by the mean reduction in total Hamilton Depression Rating Score, percentage of responders and patients in remission, Clinical Global Impression severity of illness and global improvement scores, and the Montgomery-Asberg Depression Rating Scale. A sub-analysis of patients with severe depression showed Vestra to have superior efficacy compared to fluoxetine. Both treatments resulted in improvement in Social Adaption Self-evaluation Scale total scores; however, the improvement was more evident in patients who received Vestra and achieved remission.

Vestra: What the Patient Should Know

Although clinical trials have shown a reduced risk for nausea, diarrhea, and somnolence with Vestra compared with fluoxetine, the patient should be aware that an increase in risk for dry mouth, constipation, hypotension, paresthesia, urinary hesitancy, and flushing was observed with Vestra in the trials.

* Researchers at the New York State Psychiatric Institute reviewed findings from 15 controlled studies on the use of anticonvulsants, lithium, fenfluramine and antidepressants in bulimia patients to reach their conclusions; patients in the studies used vomiting to compensate for food intake, were of normal weight, were predominately female, and were young adults.

* Found that only antidepressant therapy – particularly with fluoxetine – was consistently shown to reduce the frequency of binge eating among normal-weight patients with bulimia nervosa.

* Authors suggest that bulimia patients should demonstrate six months of real improvement before any effort is made to discontinue any antidepressant drug therapy.

Answer. There is unfortunately very little known about the effects of sertraline [Zoloft] in human pregnancy. The standard medical advice is to avoid any medication, if possible, during the first three months of pregnancy, since this is the period of greatest organ development in the developing fetus. After the first trimester, most antidepressants would pose very little risk to the fetus or mother, and what little risk there is must be carefully weighed against the risk of recurrent major depression.

The makers of Zoloft cite studies on animals in their product information, but, frankly, I doubt this is of great use to potential human mothers. It may be more useful to look at a study of a closely related (though not identical) antidepressant, Prozac [fluoxetine], which has been studied in pregnant women taking this agent during the first trimester. The study (by Pastuszak et al, JAMA, 1993) found no evidence of teratogenicity (birth defects) in the pregnant women taking Prozac, compared to a control group. There was a trend toward a higher miscarriage rate among those taking Prozac, but the risk was relatively small. Depression itself can also increase the risk of miscarriage. If these results are comparable to those with Zoloft, the risk of using either medication during pregnancy would be very small – but as yet, we don’t know. I would discuss the risks and benefits very carefully with your psychiatrist and obstetrician, and go from there.

Answer. I can’t tell you with any degree of confidence whether, in your case, there is a “link” between your taking Prozac and the pain you describe. (Did the aches and pains begin soon after you started the Prozac? This would be an important question to answer). There are many causes of lower back pain and aches and pains – Prozac would be a relatively rare cause, but a few cases have been reported. In one case, however, the joint pain was accompanied by fever, skin rash, and swollen lymph glands – which is not what you are describing. There is also a case report of Prozac actually improving arthritis.

I suggest you discuss this question with the physician who is prescribing the Prozac, and consider consulting a rheumatologist if you have not already done so. If the Prozac is implicated, changing to a different antidepressant may be warranted.

Side effects include nausea, dry mouth, and sleepiness. As with all SSRIs, citalopram should not be taken with monoamine oxidase inhibitors.