Sertraline hydrochloride (trade name «Zoloft») is an antidepressant of selective serotonin reuptake inhibitor group (SSRI). Canadian Pharmacy Generic Zoloft is primarily issued in cases of major depression at adult outpatients as well as obsessive-compulsive disorders, panic attacks and social anxiety disorders at adults and children.
Panic disorders treatment with Zoloft show significant anxiety attacks decrease and quality of life improvement. At obsessive-compulsive disorders, Sertraline is not as effective as cognitive-behavioral therapy. Best results were achieved in a combination of these two methods.
Generic Zoloft also relieves late luteal phase dysphoric disorder symptoms and can be used in sub-therapeutic doses or intermittently during treatment.
Zoloft history begins in 1970, when «Pfizer’s» chemist Reinhard Sarges invented a new range of psychoactive compounds based on chlorprothixene and thiothixene neuroleptics structure. Further work on these compounds development led to tametraline, norepinephrine and weaker dopamine reuptake inhibitors creation. Tametraline development was soon frozen due to adverse stimulatory effects observed at animals.
A few years later, in 1977, pharmacologist Kenneth Koe, after comparing structural features of various reuptake inhibitors, became interested in tametraline agents. He asked another «Pfizer’s» chemist, Willard Welch, to synthesize some of the previously unknown tametraline derivatives. As a result, Welch created a number of potent norepinephrine and triple reuptake inhibitors, but, to scientists astonishment, one of the usually inactive cis-analogs became a serotonin reuptake inhibitor. Welch then prepared stereoisomers of these compounds which were tested in vivo by scientist Albert Wiseman, specializing on animal behavior. Most potent and selective (+) – isomer, which it was decided to work with further, is called Sertraline. Weissman and Koe recall that this group of substances was not created with a purpose to create an antidepressant such as SSRIs, and in this sense, their discovery was not «purpose intended», and thus a creation of Sertraline molecule was a happy incidence.
In 1991 Zoloft was approved by US FDA on basis of Psychopharmacological Drugs Advisory Committee recommendations. The previous year, the drug has become already available in the UK market. FDA Committee agreed that Zoloft proved to be safe and effective drug for depression treatment.
Until 2002, Zoloft was approved only for use among patients over 18 years old; the same year it was approved by FDA for children aged 6 years and older with severe obsessive-compulsive disorders (OCD).
In 2005, FDA made it mandatory for all antidepressants manufacturers, including Zoloft, to print on packages black boxed warning about the possibility of causing suicidal behavior among children. In 2007, this marking was changed again, and it included a warning about the possibility of suicidal behavior among young adults aged 18 – 24 years.
Mechanism of Action
Sertraline is mainly a selective serotonin reuptake inhibitor (SRI), with a binding affinity (Ki) equal to 3.3 nm. Therapeutic generic Zoloft dosage (50-200 mg/day), taken during four weeks, caused 80 – 90% serotonin transporter (SERT) inhibition in brain striatum, estimated by positron emission tomography. Daily Zoloft dose of 9 mg intake was sufficient for 50% SERT inhibition.
Generic Zoloft is used to treat a number of diseases, including:
- obsessive-compulsive disorder (OCD);
- body dysphoric disorder (BDD);
- posttraumatic stress disorder (PTSD);
- premenstrual dysphoric disorder (PMDD);
- panic attacks;
- social phobia (social anxiety).
- the drug is also used to treat premature ejaculation and vascular headaches, but its efficacy in treating these diseases proof is less reliable.
Original presales clinical trials have shown that Canadian Pharmacy Zoloft shows mild to moderate effectiveness in depression treatment. However, many more recent studies indicate that the drug may be used as one of medication of choice for depression treatment for outpatients. Despite negative results of earlier studies, Zoloft is also frequently used to treat inpatients with depression. Generic Zoloft (Sertraline) is effective in case of severe depression as well as dysthymia – more chronic and mild depression.
At depression treatment, accompanied by obsessive-compulsive disorder, Sertraline demonstrated a significant advantage compared with desipramine (Norpramin) both in case of obsessive-compulsive disorder and depression. At depression treatment accompanied by panic disorder equivalence of Sertraline and imipramine has been observed, with Sertraline had a significantly better tolerability. At patients with depression with concomitant personality disorders, Zoloft showed improvement of personality traits and this improvement practically does not depend on depression course.
Depression among Elderly People
Sertraline for depression treatment among elderly people (over 60 years) is much more effective than placebo and comparable with other SSRIs – Fluoxetine and TCAs Amitriptyline, Nortriptyline (Pamelor) and Imipramine. Canadian Zoloft has a much lower side effects incidence than TCAs, except for sickness, which is often observed when taking Sertraline. Moreover, for patients over 70 years, Zoloft is more effective than Fluoxetine or Nortriptyline. Test in 2003, comparing Zoloft and placebo among elderly patients showed statistically significant (i. e., with a small probability of incident), but clinically very insignificant improvements in cases of depression, without improving quality of life.
Placebo-controlled trials have demonstrated that generic Zoloft is effective for treating obsessive-compulsive disorders at adults and children. The drug has a better tolerability and based on treatment analysis, in general, shows itself in more favorable light in comparison with OCD treatment«golden standard» – Clomipramine drug. Zoloft also showed itself slightly more effective than Fluoxetine (Prozac). It is believed that for obsessive-compulsive disorder effective treatment, a higher Sertraline dosage than usual dosage for depression treatment is necessary.
In course of four large double-blind studies, Canadian Pharmacy Zoloft displayed its superiority over placebo in panic disorder treatment. The response rate was not dependent on dosage (50 – 200 mg). In addition to panic attacks frequency reduction by about 80% and general anxiety reduction, Sertraline caused the quality of life improvement in most parameters. Patients whose condition while taking Zoloft was classified as «improved», reported improved quality of life. Generic Zoloft showed similar efficacy among both men and women, as well as patients with agoraphobia and without it.
Social Anxiety Disorder
Sertraline has been successfully used for social phobia treatment (social anxiety disorder). A study with flexible Zoloft dosage has shown that for adequate response a higher dose range requires. A more desirable response was observed at patients with late-onset disorders, especially at adult patients. The greatest improvement in the quality of life was observed among patients with more severe disorders. In addition to social phobia psychological components, such as fear and avoidance, Zoloft also causes some physiological components improvement, such as heartbeat and rush, but has no effect on symptoms such as sweating and shivering.
Late Luteal Phase Dysphoric Disorder
According to several double-blind studies, Sertraline is an effective drug to relieve premenstrual dysphoric disorder symptoms – a severe form of premenstrual syndrome. Significant improvement was observed in 50-60% of children. The improvement as displayed during the first week of treatment, in addition to improved mood, reduced anxiety and irritability, improved social and family functions and overall quality of life. Activity functions and physical symptoms such as edema, abdominal and breast distension are less dependent on Canadian Zoloft effect. Despite certain sexual side effects of Zoloft, Sertraline group, unlike placebo group, experienced a significant improvement in sexual functions.
Posttraumatic Stress Disorder
Two double-blind placebo-controlled studies have confirmed Zoloft efficacy in severe chronic PTSD treatment at individuals with average disease duration of more than ten years. Physical or sexual abuse was observed at more than 60% of patients, 75% of whom were women. During 12-week period, 53 – 60% of patients treated with Canadian Zoloft showed a significant or very significant improvement. Some participants in both trials continued treatment for another year. The authors noted that the drug acts slower at patients with more severe symptoms.
Sexual Function Side Effects
As when taking other SSRIs, Zoloft is associated with sexual side effects, including sexual excitement disorders and difficulties with achieving orgasm. Several double-blind studies of Zoloft sexual side effects vs. placebo or other antidepressants were conducted. 67% of men taking generic Zoloft, reported difficulties with ejaculation, compared with 18% before treatment. Moreover, the group of women, who did not have originally difficulties with achieving orgasm, 41% began to experience such difficulties after Zoloft application. In another study, a mixed group experienced 40% level of orgasmic dysfunction when taking Zoloft. Sexual excitement disorder, defined as «insufficient lubrication for women and erectile dysfunction for men» have been observed in 12% of patients treated with Canadian Zoloft. Improved mood while taking Sertraline sometimes compensates these side effects, and sexual desire and overall sex satisfaction are the same as they were before receiving the drug. Such side effects as genital anesthesia, loss or reduction of reaction to sexual stimuli and ejaculatory anhedonia, are possible. While these effects are generally reversible, they can sometimes be long-lasting, persisting even after drug withdrawal. This phenomenon is called «post-SSRI sexual dysfunction».
FDA requires that all antidepressants packages, including Sertraline, contain a black boxed warning that patients younger than 25 years taking antidepressants may be more exposed to the risk of suicide. This warning is based on data received from statistical analyses carried out by two independent FDA expert groups, which showed a 2-fold increase in suicidal thoughts and behavior among children and adolescents, as well as a 1.5-fold increase in suicidal behavior among patients aged 18 – 24 years. During clinical trials, suicidal thoughts and behavior were observed extremely rare.
Zoloft Withdrawal Syndrome
Sudden Zoloft (Sertraline) discontinuation may lead to withdrawal syndrome development. During a blind study, this syndrome was observed in 60% of patients with depression taking generic Zoloft. During 5 – 8 day period when Zoloft was temporarily replaced by placebo, most common symptoms (reported by more than a quarter of patients) were:
- emotional instability;
About a third of patients reported mood decrease at the level usually associated with the major depressive episode.