Adverse events mild, moderate, severe

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

The most frequent adverse reactions were dry mouth, somnolence/sedation, asthenia (weakness, fatigue or tiredness) and dizziness. Three-quarters of the patients rated the events as mild to moderate, and one-quarter of the patients rated the events as being severe. These events appeared to be dose related. 

Regarding side-effect profiles, all three SSNRIs are generally well tolerated, most adverse events occurring early in treatment, with a mild to moderate severity and a tendency to decrease or disappear with continued treatment. Venlafaxine (1) seems to be the least weU-toIerated SNRI, combining a higher level of serotonergic adverse events (nausea, sexual dysfunction, withdrawal problems) with dose-dependent hypertension. In contrast, milnacipran (2) and duloxetine (3) appear better tolerated and essentially devoid of cardiovascular toxicity. 

The efficacy of olanzapine monotherapy for the acute hypomania or mania has also been studied in a consecutive series of 15 patients entering an open, uncontrolled, 8-week trial of olanzapine monotherapy (40). Most of the patients had significant reductions in mania rating and more limited improvement in depression rating, but more reported adverse events, consistent with other studies The most commonly reported adverse effects were moderate to severe dry mouth (80%), weight gain (77%), mild dizziness (60%), edema (53%), mild to moderate drowsiness (53%), and constipation (47%). 

The majority of gemifloxacin adverse reactions experienced by patients in clinical trials were considered to be of mild to moderate severity, primarily due to rash (0.8% of patients), nausea (0.3%), diarrhea (0.3%), urticaria (0.2%), and vomiting (0.2%). Most of the postmarketing adverse events reported were cutaneous and most of these were rash. Some of these cutaneous adverse events were considered serious. The majority of rashes occurred in women and in patients under 40 years of age. 

In 3995 patients who took azithromycin 1.5 g in divided doses over 5 days or who took 1 g as a single dose for urethritis/cervicitis adverse events occurred in 12% (1). In patients over 65 years the rate was 9.3%, and in children under 14 years of age it was 5.4%. The most common adverse effects were gastrointestinal (9.6%) central nervous system and peripheral nervous system effects were reported in 1.3%. Overall, 59% of the adverse events were considered mild, 34% moderate, and only 6% severe, involving mainly the gastrointestinal tract. Adverse events resulted in withdrawal in 0.7% of patients, lower than the rate reported with other macro-lides. Treatment-related rises in liver enzymes were uncommon (under 2%), as was leukopenia (1.1-1.5%). 

Adverse effects of dirithromycin were studied in 4263 patients (1). There was abdominal pain in 5.6%, diarrhea in 5.0%, and nausea in 4.9%. Headache was relatively common (4.5%). In 63% of cases the adverse events were considered mild, in 31% moderate, and in 6.3% severe. Adverse events resulted in withdrawal in 3.1%, mainly because of gastrointestinal symptoms such as nausea and abdominal pain. 

In 66 patients with severe psoriasis who took fumaric acid esters for up to 14 years, there were adverse events in 73%, usually mild and mainly consisting of flushing (55%), diarrhea (42%), nausea (14%), tiredness (14%), and stomach complaints (12%) (8). There was a relative lymphocytopenia in 76%, resulting in permanent withdrawal in four patients. There were transient eosinophUia in 14%, and moderate Uver enzyme rises were observed in 25%. 

In a randomized study in 956 volunteers aged 17-72 years a shortened immunization schedule of injections at 0, 1, and 2 months were compared with a schedule of injections at 0,1, and 12 months (16). Adverse events were transient and mild to moderate. Soreness was the most frequently reported local symptom (82%), whereas fatigue (20-22%) was the most frequently reported general symptom. Two volunteers had more serious adverse events severe chills and shaking in one and an episode of syncope (lasting a few minutes with complete recovery) on the day of the first dose in another. The authors concluded that doses at 0, 1, and 2 months would provide protection during a typical tick-transmission season. 

In 631 adult patients with moderate to severe atopic dermatitis enrolled in a randomized, double-blind, multicenter comparison of tacrolimus (0.03% or 0.1%) with a vehicle applied twice-daily for 12 weeks, the most common adverse events were skin burning, erythema, and pruritus (83). Others were flu-like symptoms and headache. Withdrawal was required in 50 patients because of adverse events, twice as many as in the vehicle group. There was pruritus in 30 patients, skin burning in 19, skin erythema in 12, and skin infections in two. Skin burning and pruritus have consistently been observed with tacrolimus ointment, typically during the first days of treatment, reducing in incidence within the first week they tend to be mild or moderate. 

This scale is best defined as one in which an ordering of values can be assigned. Examples of data from clinical studies measured on an ordinal scale include severity of an adverse event classified as mild, moderate, or severe age categorized as < 65, 65-70, 71-75, and > 75 years. The ordinal nature of the measurement scales means that we can say that a mild headache is less severe than a moderate headache, which is less severe than a severe headache. However, we cannot say that the difference between mild and moderate is the same as the difference between moderate and severe. 

I Adverse Effects. The most frequently reported adverse effects of tiagabine are dizziness, asthenia, nervousness, tremor, diarrhea, and depression. Rash is uncommon with tiagabine. Adverse events usually are mild to moderate in severity and transient, and most were associated with dose titration. CNS side effects may be diminished by taking tiagabine with food, thus slowing the absorption rate. Serious adverse events were uncommon, and no idiosyncratic events, including visual field defects, were reported. " ... 

All 52 patients received a unit dosage of lOOmg/day of kava extract. The treatment duration varied across subjects, with a mean of about 51 days across the total sample. The patients rated their treatment outcome on the Global Improvement Scale using a five-point rating system. Physicians rated the three target symptoms (anxiety, tension, and restlessness) on a four-point scale not present, mild, moderate, and severe. In addition, information on adverse events was obtained through a questionnaire. 

No serious adverse events related to rAHF-PFM were reported in the Pivotal study. In total, 19 non-serious adverse events in seven patients were judged to be product-related these included taste perversion, headache, fever, diarrhea, dizziness, hot flashes, pain in upper abdomen, pain in lower chest, shortness of breath, sweating, nausea, rigors, and itching in the arm used for the infusion [8]. Five non-serious drag-related events were mild, 12 were moderate, and two (one high fever and one severe headache, reported concurrently in one patient) were severe. No patient withdrew from the study because of any study-drag-related adverse event [8, 25, 27-29],... 

Of the non-serious adverse events reported, seven have been deemed related to rAHF-PFM (four moderate, one mild, and two severe events which consisted of decreased coagulation FVIII level and unspecified hematoma). 

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