Saturday, September 29, 2012

treatment of premature ejaculation in men.

Dapoxetine



From Wikipedia, the free encyclopedia



Dapoxetine (INN, brand names Kutub and Priligy) is a short-acting selective serotonin reuptake inhibitor (SSRI) marketed for the treatment of premature ejaculation in men.[1] Dapoxetine is the only drug with regulatory approval for such an indication. Currently, it is approved in several European countries, including Finland, Sweden, Spain, Portugal, Germany, Italy, Czech Republic and Austria.[2][3][4] It is also available by prescription in New Zealand and South Korea. Dapoxetine is also being considered for approval in other European countries. In the United States, Dapoxetine has been in Phase III trials of the U.S. Food and Drug Administration (FDA) approval process since 2005.[5]

Several studies have suggested that dapoxetine has a benefit in the treatment of premature ejaculation.[6] In a report published in the British Journal of Urology based on data from the phase III trial, authors conclude that dapoxetine is well-tolerated and improved measures associated with premature ejaculation, including reduction of personal distress, interpersonal difficulty and improvement in the satisfaction with the sexual intercourse.[7]

History

Dapoxetine was discovered by Eli Lilly and Company. Originally known as LY 210448, it was being developed by Lilly as an antidepressant. Eli Lilly sold the patent to Johnson & Johnson for $65 million and future royalties in December 2003. In 2004, dapoxetine was submitted to the FDA in the form of dapoxetine hydrochloride by the ALZA Corporation and its parent company, Johnson & Johnson, for the treatment of premature ejaculation with a New Drug Application (NDA). However, the FDA issued a "not approvable" letter for dapoxetine, requiring additional clinical study.[8] Two further clinical trials were completed in 2006, and approval is under review by the FDA.
Dapoxetine has been submitted for approval in the European Union and is being reviewed. In 2009, dapoxetine received approval in Sweden, Finland, Spain, Portugal, Germany, Austria, Italy, and New Zealand. Approvals for dapoxetine are also anticipated in other European countries as well. In addition, filings for approval have been submitted in Canada, Australia, Mexico, Turkey, and six other countries.[5]
By
WebMD Health News
Reviewed byLouise Chang, MD

Sept. 7, 2006 -- The first drug developed specifically for premature ejaculation performed well in two clinical trials, but the new treatment probably won't be available in the U.S any time soon.
Men in the study who took the experimental drug Dapoxetine, developed by Johnson & Johnson Pharmaceuticals in conjunction with ALZA Corp., were able to maintain erections longer than men who took placebos.
Dapoxetine is a selective serotonin reuptake inhibitor (SSRI) but is slightly different from the SSRIs (such as Zoloft, Paxil, and Prozac) widely prescribed for depression and other psychiatric disorders.
The drug was designed to be taken as needed, one to three hours before sex, instead of every day. Also, it is eliminated from the body more quickly than other SSRIs.
Hopes that Dapoxetine would become the first drug approved for premature ejaculation dimmed last October, when the FDA sent a "not approvable" letter to the manufacturer.
The FDA's concerns about the drug were not made public. In a news release, ALZA Corp. promised to "address questions raised in the FDA letter."
A spokesperson for Johnson & Johnson told WebMD Thursday that the company "remains committed to the global development" of Dapoxetine.

A Common Complaint

Although it is rarely talked about, premature ejaculation is a common problem, affecting as many as a third of men.
Far fewer men seek treatment, however.
Those who do are often advised on practice techniques to help. Some receive a prescription for a traditional, long-acting SSRI, since delayed ejaculation is a common side effect among men who take SSRIs for depression.
This use of traditional SSRIs would be considered off-label since the medications are not specifically indicated for this problem.
Other potential sexual side effects of SSRIs include erectile dysfunction and loss of libido, however, making the traditionalantidepressants less than ideal for treatment of premature ejaculation, Jon L. Pryor, MD, tells WebMD. Pryor is a urology professor at the University of Minnesota.

Longer-Lasting Sex

In the manufacturer-funded study, Pryor and colleagues compared 30-milligram and 60-milligram doses of Dapoxetine to a placebo in roughly 2,600 men with moderate to severe premature ejaculation.
Prior to treatment, the men's average ejaculation time was just under a minute.
With treatment, the average time to ejaculation was 1.75 minutes in the placebo-treated men, 2.78 minutes in the men treated with 30 milligrams of Dapoxetine, and 3.32 minutes in the men treated with 60 milligrams of the drug. The study lasted three months.
"A couple of minutes may not sound like much but for these guys it was huge," Pryor says.
Men who took the short-acting SSRI also reported having more control over their ejaculations than the placebo-treated men; and they and their female partners reported improved sexual satisfaction.
Pryor says an effective, specific treatment could do for premature ejaculation what Viagra did for erectile dysfunction-- taking away the 'snicker' factor by stimulating open discussion about the disorder.


"Viagra wasn't a magic pill, but it did bring ED into the open and men who had it learned that they were not alone," he says. "The discussion that followed stimulated research that led to other treatments.
"Premature ejaculation is more common than ED, but no one talks about it," adds Pryor.
Ira Sharlip, MD, a urology professor at the University of California, San Francisco, tells WebMD there is a definite need for an effective treatment for premature ejaculation.
"I have patients who are really disturbed by this issue, and so are their wives," he says. "The current treatments are far from perfect."
Sharlip says traditional SSRIs work best when they are taken every day, and even then they only work for around two-thirds of patients.
"Premature ejaculation is certainly one of the most common forms of sexual dysfunction among men," Sharlip says. "Not everyone who has it is bothered by it, but for those who are, it can be a very big problem."

Myths surrounding premature ejaculation

  • Myth:
    Premature ejaculation is a problem that is entirely in one’s mind.
  • Fact:
    New studies have shown that a low level of serotonin, a natural substance that is produced by nerves, may be a possible cause.
  • Myth:
    Alcohol is a good method for controlling premature ejaculation.
  • Fact:
    It is not an effective treatment for premature ejaculation.

PE is a very real condition with real impact on people's life. It is now much better understood and treated than in the past. Help is available for you and your partner to find a way round this problem

Warnings And Precautions:
General:
dapoxetine is only indicated in men with PE. Safety has not been established and there are no data on the ejaculation-delaying effects in men without PE.
Use with recreational drugs:
Patients should be advised not to use dapoxetine in combination with recreational drugs. Recreational drugs with serotonergic activity such as ketamine, methylenedioxymethamphetamine (MDMA) and lysergic acid diethylamide (LSD) may lead to potentially serious reactions if combined with dapoxetine. These reactions include, but are not limited to, arrhythmia, hyperthermia, and serotonin syndrome. Use of dapoxetine with recreational drugs with sedative properties such as narcotics and benzodiazepines may further increase somnolence and dizziness.
Ethanol:
Combining alcohol with dapoxetine may increase alcohol-related neurocognitive effects and may also enhance neurocardiogenic adverse events such as syncope, thereby increasing the risk of accidental injury; therefore, patients should be advised to avoid alcohol while taking dapoxetine.
Syncope:
The frequency of syncope characterized as loss of consciousness in the dapoxetine clinical development program varied depending on the population studied and ranged from 0.06% (30 mg) to 0.23% (60 mg) for subjects enrolled in the Phase 3 placebo-controlled clinical trials to 0.64% (all doses combined) for Phase 1 non-PE healthy volunteer studies. Possibly prodromal symptoms such as nausea, dizziness/lightheadedness, and diaphoresis were reported more frequently among patients treated with dapoxetine compared to placebo. In patients receiving 30 mg dapoxetine in Phase 3 clinical trials, nausea was reported in 11.0%, dizziness in 5.8% and hyperhidrosis/diaphoresis in 0.8%. In patients receiving 60 mg dapoxetine in Phase 3 clinical trials, nausea was reported in 21.2%, dizziness in 11.7% and hyperhidrosis/diaphoresis in 1.5%. In addition, the occurrence of syncope and possibly prodromal symptoms appears dose dependent as demonstrated by higher incidence among patients treated with higher than recommended doses in Phase 3 clinical trials. Cases of syncope characterized as loss of consciousness observed in the clinical trials were considered vasovagal in etiology and the majority occurred during the first 3 hours after dosing, after the first dose, or associated with study-related procedures in the clinic setting (such as blood draw and orthostatic maneuvers and blood pressure measurements). Possibly prodromal symptoms, such as nausea, dizziness, lightheadedness, palpitations, asthenia, confusion and diaphoresis generally occurred within the first 3 hours following dosing, and often preceded the syncope. Patients need to be made aware that they could experience syncope at any time with or without prodromal symptoms during their treatment with dapoxetine. Prescribers should counsel patients about the importance of maintaining adequate hydration and about how to recognize prodromal signs and symptoms to decrease the likelihood of serious injury associated with falls due to loss of consciousness. If the patient experiences possibly prodromal symptoms, the patient should immediately lie down so his head is lower than the rest of his body or sit down with his head between his knees until the symptoms pass, and be cautioned to avoid situations where injury could result, including driving or operating hazardous machinery, should syncope or other CNS effects occur. Combining alcohol with dapoxetine may enhance neurocardiogenic adverse events such as syncope, thereby increasing the risk of accidental injury; therefore, patients should be advised to avoid alcohol while taking dapoxetine. Subjects with underlying cardiovascular disease were excluded from Phase 3 clinical trials. The risk of adverse cardiovascular outcomes from syncope (cardiac syncope and syncope from other causes) is increased in patients with underlying structural cardiovascular disease (e.g., documented outflow obstruction, valvular heart disease, carotid stenosis and coronary artery disease). There are insufficient data to determine whether this increased risk extends to vasovagal syncope in patients with underlying cardiovascular disease. Orthostatic hypotension: An orthostatic test should be performed before initiating therapy. In case of a history of documented or suspected orthostatic reaction, treatment with dapoxetine should be avoided. Orthostatic hypotension has been reported in clinical trials. The prescriber should counsel the patient in advance that if he experiences possibly prodromal symptoms, such as lightheadedness soon after standing, he should immediately lie down so his head is lower than the rest of his body or sit down with his head between his knees until the symptoms pass. The prescriber should also inform the patient not to rise quickly after prolonged lying or sitting. In addition, dapoxetine should be prescribed with caution in patients taking medicinal products with vasodilatation properties (such as alpha adrenergic receptor antagonists, nitrates, PDE5 inhibitors) due to possible reduced orthostatic tolerance.
Moderate CYP3A4 inhibitors:
Caution is advised in patients taking moderate CYP3A4 inhibitors and the dose is restricted to 30 mg.
Potent CYP2D6 inhibitors:
Caution is advised if increasing the dose to 60 mg in patients taking potent CYP2D6 inhibitors or if increasing the dose to 60 mg in patients known to be of CYP2D6 poor metabolizer genotype, as this may increase exposure levels, which may result in a higher incidence and severity of dose dependent adverse events.
Suicide/suicidal thoughts:
Antidepressants, including SSRIs, increased the risk compared to placebo of suicidal thinking and suicidality in short-term studies in children and adolescents with Major Depressive Disorder and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24. In clinical trials with dapoxetine for the treatment of premature ejaculation, there was no clear indication of treatment-emergent suicidality.
Mania:
dapoxetine should not be used in patients with a history of mania/hypomania or bipolar disorder and should be discontinued in any patient who develops symptoms of these disorders. Seizure: Due to the potential of SSRIs to lower the seizure threshold, dapoxetine should be discontinued in any patient who develops seizures and avoided in patients with unstable epilepsy. Patients with controlled epilepsy should be carefully monitored. Use in children and adolescents under age 18: dapoxetine should not be used in individuals below 18 years of age.
Co-morbid depression and psychiatric disorders:
Men with underlying signs and symptoms of depression should be evaluated prior to treatment with dapoxetine to rule out undiagnosed depressive disorders. Concomitant treatment of dapoxetine with antidepressants, including SSRIs and SNRIs, is contraindicated. Discontinuation of treatment for ongoing depression or anxiety in order to initiate dapoxetine for the treatment of PE is not recommended. Dapoxetine is not indicated for psychiatric disorders and should not be used in men with these disorders, such as schizophrenia, or in those suffering with co-morbid depression, as worsening of symptoms associated with depression cannot be excluded. This could be the result of underlying psychiatric disorder or might be a result of medicinal product therapy. Physicians should encourage patients to report any distressing thoughts or feelings at any time and if signs and symptoms of depression develop during treatment, dapoxetine should be discontinued.
Haemorrhage:
There have been reports of bleeding abnormalities with SSRIs. Caution is advised in patients taking dapoxetine, particularly in concomitant use with medicinal products known to affect platelet function (e.g., atypical antipsychotics and phenothiazines, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs [NSAIDs], anti-platelet agents) or anticoagulants (e.g., warfarin), as well as in patients with a history of bleeding or coagulation disorders.
Renal impairment:
dapoxetine is not recommended for use in patients with severe renal impairment and caution is advised in patients with mild or moderate renal impairment.
Withdrawal effects:
Abrupt discontinuation of chronically administered SSRIs used to treat chronic depressive disorders has been reported to result in the following symptoms: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia and hypomania. However, a double-blind clinical trial in subjects with PE designed to assess the withdrawal effects of 62 days of daily or as needed dosing with 60 mg dapoxetine showed no evidence of withdrawal syndrome and little evidence of withdrawal symptoms with only a slightly higher incidence of mild or moderate insomnia and dizziness reported in subjects switched to placebo after daily dosing. Consistent results were seen in a second double-blind clinical trial with a 24-week treatment phase of 30 and 60 mg doses as needed followed by a 1-week withdrawal assessment period.
Lactose intolerance:
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Potential for interaction with monoamine oxidase inhibitors:
In patients receiving an SSRI in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued an SSRI and have been started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Animal data on the effects of combined use of an SSRI and MAOIs suggest that these medicinal products may act synergistically to elevate blood pressure and evoke behavioural excitation. Therefore, dapoxetine should not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, an MAOI should not be administered within 7 days after dapoxetine has been discontinued.
Potential for interaction with thioridazine:
Thioridazine administration alone produces prolongation of the QTc interval, which is associated with serious ventricular arrhythmias. Medicinal products such as dapoxetine that inhibit the CYP2D6 isoenzyme appear to inhibit the metabolism of thioridazine and the resulting elevated levels of thioridazine are expected to augment the prolongation of the QTc interval. Dapoxetine should not be used in combination with thioridazine or within 14 days of discontinuing treatment with thioridazine. Similarly, thioridazine should not be administered within 7 days after dapoxetine has been discontinued.
Medicinal/herbal products with serotonergic effects:
As with other SSRIs, co-administration with serotonergic medicinal/herbal products (including MAOIs, L-tryptophan, triptans, tramadol, linezolid, SSRIs, SNRIs, lithium and St. John's Wort(Hypericum perforatum) preparations) may lead to an incidence of serotonin associated effects. Dapoxetine should not be used in combination with other SSRIs, MAOIs or other serotonergic medicinal/herbal products or within 14 days of discontinuing treatment with these medicinal/herbal products. Similarly, these medicinal/herbal products should not be administered within 7 days after dapoxetine has been discontinued.
CNS active medicinal products:
The use of dapoxetine in combination with CNS active medicinal products has not been systematically evaluated in patients with premature ejaculation. Consequently, caution is advised if the concomitant administration of dapoxetine and such medicinal products is required.
Effects of co-administered medicinal products on the pharmacokinetics of Dapoxetine:
In vitro studies in human liver, kidney, and intestinal microsomes indicate dapoxetine is metabolized primarily by CYP2D6, CYP3A4 and flavin monooxygenase 1 (FMO1). Therefore, inhibitors of these enzymes may reduce dapoxetine clearance.
CYP3A4 inhibitors:
Potent CYP3A4 inhibitors -Administration of ketoconazole (200 mg twice daily for 7 days) increased the C-max and AUC(inf) of dapoxetine (60 mg single dose) by 35% and 99%, respectively. Considering the contribution of both unbound dapoxetine and desmethyldapoxetine, the Cmax of the active fraction may be increased by approximately 25% and the AUC of the active fraction may be doubled if taken with potent CYP3A4 inhibitors. The increases in the Cmax and AUC of the active fraction may be markedly increased in a part of the population which lack a functional CYP2D6 enzyme, i.e., CYP2D6 poor metabolizers, or in combination with potent inhibitors of CYP2D6.
Therefore, concomitant use of dapoxetine and potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir and atazanavir, is contraindicated.
Moderate CYP3A4 inhibitors:
Concomitant treatment with moderate CYP3A4 inhibitors (e.g., erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil, diltiazem) may also give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers. The maximum dose of dapoxetine should be 30 mg if dapoxetine is combined with any of these drugs.
These two measures apply to all patients unless the patient has been verified to be a CYP2D6 extensive metabolizer by geno- or phenotyping. In patients verified to be CYP2D6 extensive metabolizers, a maximum dose of 30 mg is advised if dapoxetine is combined with a potent CYP3A4 inhibitor and caution is advised if dapoxetine in 60 mg doses is taken concomitantly with a moderate CYP3A4 inhibitor.
Potent CYP2D6 inhibitors:
The Cmax and AUC(inf) of dapoxetine (60 mg single dose) increased by 50% and 88%, respectively, in the presence of fluoxetine (60 mg/day for 7 days). Considering the contribution of both unbound dapoxetine and desmethyldapoxetine, the Cmax of the active fraction may be increased by approximately 50% and the AUC of the active fraction may be doubled if taken with potent CYP2D6 inhibitors. These increases in the Cmax and AUC of the active fraction are similar to those expected for CYP2D6 poor metabolizers and may result in a higher incidence and severity of dose dependent adverse events.
PDE5 inhibitors:
The pharmacokinetics of dapoxetine (60 mg) in combination with tadalafil (20 mg) and sildenafil (100 mg) were evaluated in a single dose crossover study. Tadalafil did not affect the pharmacokinetics of dapoxetine. Sildenafil caused slight changes in dapoxetine pharmacokinetics (22% increase in AUCinf and 4% increase in Cmax), which are not expected to be clinically significant. However, dapoxetine should be prescribed with caution in patients who use PDE5 inhibitors due to possible reduced orthostatic tolerance.
Tamsulosin:
Concomitant administration of single or multiple doses of 30 mg or 60 mg dapoxetine to patients receiving daily doses of tamsulosin did not result in changes in the pharmacokinetics of tamsulosin. The addition of dapoxetine to tamsulosin did not result in a change in the orthostatic profile and there were no differences in orthostatic effects between tamsulosin combined with either 30 or 60 mg dapoxetine and tamsulosin alone; however, dapoxetine should be prescribed with caution in patients who use alpha adrenergic receptor antagonists due to possible reduced orthostatic tolerance.
Medicinal products metabolized by CYP2D6:
Multiple doses of dapoxetine (60 mg/day for 6 days) followed by a single 50 mg dose of desipramine increased the mean Cmax and AUCinf of desipramine by approximately 11% and 19%, respectively, compared to desipramine administered alone. Dapoxetine may give rise to a similar increase in the plasma concentrations of other drugs metabolized by CYP2D6. The clinical relevance is likely to be small.
Medicinal products metabolized by CYP3A4:
Multiple dosing of dapoxetine (60 mg/day for 6 days) decreased the AUCinf of midazolam (8 mg single dose) by approximately 20% (range -60 to +18%). The clinical relevance of the effect on midazolam is likely to be small in most patients. The increase in CYP3A activity may be of clinical relevance in some individuals concomitantly treated with a medicinal product mainly metabolized by CYP3A and with a narrow therapeutic window.
Medicinal products metabolized by CYP2C19:
Multiple dosing of dapoxetine (60 mg/day for 6 days) did not inhibit the metabolism of a single 40 mg dose of omeprazole. Dapoxetine is unlikely to affect the pharmacokinetics of other CYP2C19 substrates.
Medicinal products metabolized by CYP2C9:
Multiple dosing of dapoxetine (60 mg/day for 6 days) did not affect the pharmacokinetics or pharmacodynamics of a single 5 mg dose of glyburide. Dapoxetine is unlikely to affect the pharmacokinetics of other CYP2C9 substrates.
Warfarin:
There are no data evaluating the effect of chronic use of warfarin with dapoxetine; therefore, caution is advised when dapoxetine is used in patients taking warfarin chronically. In a pharmacokinetic study, dapoxetine (60 mg/day for 6 days) did not affect the pharmacokinetics or pharmacodynamics (PT or INR) of warfarin following a single 25 mg dose.
Ethanol:
Coadministration of a single dose of ethanol, 0.5 g/kg (approximately 2 drinks), did not affect the pharmacokinetics of dapoxetine (60 mg single dose); however, dapoxetine in combination with ethanol increased somnolence and significantly decreased self-rated alertness. Pharmacodynamic measures of cognitive impairment (Digit Vigilance Speed, Digit Symbol Substitution Test) also showed an additive effect when dapoxetine was coadministered with ethanol. Concomitant use of alcohol and dapoxetine increases the chance or severity of adverse reactions such as dizziness, drowsiness, slow reflexes, or altered judgment. Combining alcohol with dapoxetine may increase these alcohol-related effects and may also enhance neurocardiogenic adverse events such as syncope, thereby increasing the risk of accidental injury; therefore, patients should be advised to avoid alcohol while taking dapoxetine.
Pregnancy and lactation:
Dapoxetine is not indicated for use by women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy or embryonal/foetal development. It is not known if either dapoxetine its metabolites are excreted in human breast milk.
Effects on ability to drive and use machines:
Dapoxetine has minor or moderate influence on the ability to drive and use machines. Dizziness, disturbance in attention, syncope, blurred vision and somnolence have been reported in subjects receiving dapoxetine in clinical trials. Therefore, patients should be warned to avoid situations where injury could result, including driving or operating hazardous machinery. Combining alcohol with dapoxetine may increase alcohol-related neurocognitive effects and may also enhance neurocardiogenic adverse events such as syncope, thereby increasing the risk of accidental injury; therefore, patients should be advised to avoid alcohol while taking dapoxetine.
Adverse effects:
The safety of dapoxetine was evaluated in 4224 subjects with premature ejaculation who participated in five double-blind, placebo-controlled clinical trials. Of the 4224 subjects, 1616 received dapoxetine30 mg as needed and 2608 received 60 mg, either as needed or once daily.
Syncope characterized as loss of consciousness has been reported in clinical trials and is considered medicinal product-related. The majority of cases occurred during the first 3 hours after dosing, after the first dose or associated with study-related procedures in the clinic setting (such as blood draw and orthostatic maneuvers and blood pressure measurements). Prodromal symptoms often preceded the syncope.
Orthostatic hypotension has been reported in clinical trials.
The most common adverse drug reactions reported during clinical trials were headache, dizziness, nausea, diarrhoea, insomnia and fatigue. The most common adverse events leading to discontinuation were nausea (2.2% of dapoxetine-treated subjects) and dizziness (1.2% of dapoxetine-treated subjects).
Overdose:
No case of overdose has been reported. There were no unexpected adverse events in a clinical pharmacology study of dapoxetine with daily doses up to 240 mg (two 120 mg doses given 3 hours apart). In general, symptoms of overdose with SSRIs include serotonin-mediated adverse reactions such as somnolence, gastrointestinal disturbances such as nausea and vomiting, tachycardia, tremor, agitation and dizziness. In cases of overdose, standard supportive measures should be adopted as required. Due to high protein binding and large volume of distribution of dapoxetine hydrochloride, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. No specific antidotes for dapoxetine are known.

References

Sunday, September 2, 2012

Why are Relationships So Difficult?

Why are Relationships So Difficult?

One of the most common questions today is: because relationships are increasingly difficult. This article is a reflection and shows the main causes of this problem that sometimes seem no solution when you simply can be solved with just an attitude ..

Surely all we’ve ever done on this question. This is one of the questions most asked since the earliest times until today.
 
Life is an evolution, as we mature, creating social circles, among other factors, are reasons why we are increasingly stressed from day to day, tired and without much time to think. This can be mitigated, of course, but people are no longer worried about it, we are concerned with time and money in your pocket.
All these factors are unfortunately influencing relationships, whether dating, friendships or even marriage, is common to find someone who says no patience to solve problems with a conversation. Often a good chat is the solution of problems which seem endless.
There are other factors which are increasingly common. One is the independence of women and the attitudes of the same. Women are increasingly closed to discuss and manage relationships with men, so they convey more confidence. The men in turn, do not feel worthy to agree with all that. Generating so many conflicts and little understanding.
Despite being a bit complicated, nobody can be happy alone, we are living in an era where the days are going faster and faster, we must unite and seek better solutions to understand, so we make our daily life more joyful and with a lot of . Let us work more closely with our partners, after all friendship, dating and marriage are not bought but earned!