Depression Symptoms Treatment

Buy Paxil Online With Low Price

Support Drug Guide: purchase the best medicine from our sponsor, online pharmacy, where you can place an order and buy cheap drugs at low prices without a prescription, worldwide delivery.
Prices for Paxil according to the dosage forms and number of pills. The more pills in a package, the lower the price for 1 pill!

The price of the product includes the shipping rate 9.95$.

Buy Paroxetine Online Without Prescription

Paroxetine is authorised in the world under the following brand names: Aropax, Paxil, Paxil CR, Pexeva, Seroxat, Seroxat CR.

Research question

Is sertraline (Zoloft) effective at improving the symptoms and reducing the functional impairment associated with premenstrual dysphoric disorder (PMDD)?

Type of article and design

Prospective, multicentre, double-blind, randomized placebo-controlled trial.

Relevance to family physicians

As defined by DSM-IV criteria, PMDD has a group of physical and behavioural symptoms that occur during the premenstrual period and are severe enough to interfere with work, usual activities, and relationships. Premenstrual syndrome (PMS), on the other hand, has milder physical and behavioural symptoms (breast tenderness, bloating, headache, and minor mood changes). Studies have documented that about 20% to 40% of women experience premenstrual symptoms, but only about 4% to 8% of women have PMDD. The quality of life of patients with PMDD would improve substantially if medical therapy could alleviate its physical and psychological symptoms and reduce functional impairment.

Recent clinical trials suggest that progesterone (Prometrium) or oral contraceptives are no more effective than placebo for treating PMDD. Although short-acting benzodiazapines, such as alprazolam (eg, Xanax), have been effective in improving symptoms, their addictive potential limits their use. Researchers have postulated that PMDD, like major depression, might be associated with neurotransmitter dysfunction. Recent clinical trials have shown improvement of PMDD symptoms with agents that block serotonin reuptake (fluoxetine [eg, Prozac], paroxetine [Paxil]), but have not addressed patient-oriented outcomes, such as changes in lifestyle, relationships, and functioning.

Premenstrual dysphoric disorder is at the more severe end of a spectrum of illness that affects many women. We suspect many of our patients endure the symptoms and that family doctors often fail to inquire because both parties want to minimize the disease, given the social stigma surrounding premenstrual symptoms. Does this trial indicate a treatment for those with severe symptoms?

Overview of study and outcomes

A total of 447 women were recruited either through advertisement or by referral from psychiatric outpatient clinics or gynecology departments. Patients had to be 24 to 45 years old, have regular menstrual cycles lasting 24 to 36 days, and have at least a 2-year history of PMDD for study entry. Patients were excluded if they met criteria for other mood, anxiety, or eating disorders in the last 6 months, had a history of alcohol or drug abuse within 12 months, or had a lifetime history of psychotic disorders or organic mental syndromes. Patients underwent two diagnostic screening assessments. Those who failed to confirm isolated luteal-phase symptoms for at least two cycles on daily symptom ratings (consistent with DSM-IV criteria for PMDD) were excluded. In all, 277 women entered the next phase of the study in which all patients received placebo for a full menstrual cycle. This phase was designed to weed out those who had an apparent response to an intervention (in this case placebo) rather than a genuine response to a therapeutic agent. Next, 243 patients were randomized in a double-blind fashion to receive either placebo or sertraline at 50 mg daily for three menstrual cycles. Sertraline doses were increased upward by 50 mg after each cycle if response was insufficient (at physicians’ discretion).

The primary end point of the study was change from baseline in patients’ total mean score in their Daily Record of Severity of Problems. This record is a 24-item questionnaire that elicits information on the physical and psychological symptoms of PMDD (DSM-IV) and on areas of functioning, such as productivity at work, home, and school and interference with hobbies, social activities, and relationships. An intent-to-treat perspective was taken in the analysis.

Secondary end points included Hamilton Rating Scale for Depression scores and response to treatment as measured by the Clinical Global Impression (CGI) scale. In addition, functional impairment affecting personal relationships and work was measured by the Social Adjustment Scale.

Results

Patients in both treatment arms were similar at baseline. Mean age of patients was 36 years, and mean duration of PMDD was 9 to 10 years. About 40% of patients had a history of major depressive disorder, and 25% had a history of postpartum depression.

The DRSP total scores decreased significantly (P<.001) in the sertraline-treated group (from 64 ± 22 to 44 ± 19, 32%) compared with the placebo-treated group (from 62 ± 22 to 54 ± 24,11%). Lower scores indicate improvement. It is interesting to note that DRSP total scores in the placebo-treated group decreased considerably from baseline to end point. The authors suggest this trend could be due to “hypervigilance” in the setting of a clinical trial. According to the CGI scale, 62% of the sertraline-treated group and 34% of the placebo-treated group responded to therapy (P<.001). Evaluation of functional impairment revealed that productivity was 38% less impaired for the sertraline group and 13% less impaired for those receiving placebo (P<.001); hobbies and social activities were hindered 38% less and 17% less (P<.002), and relationships improved by 42% and 15% (P< .001) in the sertraline-and placebo-treated groups, respectively.

Sertraline was well tolerated generally (18% of adverse events were considered severe in the sertraline group, 14% in the placebo group). Patients receiving sertraline had significantly more nausea and diarrhea and significantly lowered libido. This is useful information for patients who are prescribed sertraline regularly.

Analysis of methodology

Overall, investigators conducted a well-designed trial. Unlike many other authors investigating serotonin reuptake inhibitors (SSRIs) in PMDD, these investigators used validated instruments to measure symptoms and functional outcomes. The placebo run-in phase was valuable for differentiating true therapeutic response. Compliance was assessed by pill counts at each visit. Reasons patients dropped out were explicitly stated for each phase of the trial, and patients were appropriately accounted for throughout the trial.

Limitations of the trial include the fact that dose titration of sertraline was left to the discretion of each investigator rather than being set by more objective criteria. Interrater reliability scoring to show consistency of evaluation among various investigators was not performed. Also, investigators evaluated only the short-term (3 months) efficacy and safety of sertraline for PMDD. Long-term outcomes were not addressed.

Application to clinical practice

Certainly, nonpharmacologic approaches to managing symptoms can be tried first (diet, exercise), especially for patients with mild PMS symptoms. Psychological interventions, such as support groups and stress management, are usually helpful. Although sertraline had statistically significant results over placebo in most end points studied, it is difficult to ascertain whether these differences are truly clinically significant. Also, because head-to-head trials of other SSRIs have not been held to seek the outcomes evaluated in this trial, we cannot conclude with certainty that the benefits seen with sertraline represent an SSRI class effect.

Several issues limit generalizability of the data from this trial to the general population of women seen by family physicians. The trial did not involve women with concurrent psychiatric illnesses or women with less severe PMS symptoms; it involved patients referred from specialty psychiatric clinics and gynecology departments. The trial was performed in an environment in which compliance was intensely monitored and among women who were willing to keep regular appointments and record daily symptoms. All these factors could have contributed to a positive therapeutic response.

It is often difficult for nonexperts to judge what a few points’ difference in a cognitive-behavioural scale means clinically. For this reason, it was helpful to add the Social Adjustment Scale to indicate how depressive illness affects lifestyle and coping. The improvement in patients’ ratings and function was useful for obtaining patient-oriented evidence.

The advantages of SSRIs over other proposed PMDD therapies include a favourable side-effect profile, ease of administration (once daily dosing), and relative safety in overdose. Questions addressing appropriate duration of therapy and long-term efficacy and safety, however, await further study.

Bottom line

Sertraline appears to be well tolerated and effective for improving the symptoms and reducing the functional impairment associated with PMDD. It can be considered an effective therapeutic alternative for treating PMDD. Long-term efficacy and safety remain uncertain.