However, adverse effects were more frequent in the sildenafil and paroxetine groups compared to the squeeze technique group.
Treating Premature Ejaculation
A recent single-blind placebo-controlled clinical study compared the efficacy of on-demand treatment with paroxetine 30 mg, dapoxetine 30 mg, sildenafil 50 mg, combined dapoxetine 30 mg + sildenafil citrate 50 mg and placebo on 150 patients with PE for a period of 6 weeks [Citation88]. The authors reported significant improvement in the IELT, sexual satisfaction score and PE diagnostic tool score in all groups after treatment, with the best values reported in the combined dapoxetine + sildenafil citrate group. Another comparative study assessed the efficacy of on-demand dapoxetine 30 mg, on-demand dapoxetine 60 mg and daily paroxetine 20 mg on 150 patients with PE for a 1-month duration [Citation89]. The IELT increased by 117%, 170% and 117% from baseline to post-treatment in the 30 mg dapoxetine group, 60 mg dapoxetine group and paroxetine group; respectively. Dapoxetine was found to have an additive effect on psychotherapy for the treatment of patients with PE.
Efficacy in treatment of PE
Almost all SSRIs are dependent on liver metabolism by cytochrome P450 (CYP450) enzyme isoforms each with a distinct profile of inhibition (). When SSRIs are co-administered with drugs that are metabolised by a specific CYP450 enzyme, they compete for binding to the active site of the enzyme [Citation90], inhibiting the metabolism of the other drug substrates and elevating their plasma levels. This prolonged drug action can place patients at increased risk of drug toxicity. This drug interaction is often faced when SSRIs are co-administered with psychiatric drugs, as well as other medications given for a variety of medical conditions. The SSRIs are not uncommonly combined with TCAs to treat psychiatric patients.
Erectile Dysfunction Medication
As both drug classes are metabolised by CYP450 enzymes, the resulting interaction is well documented and increased plasma concentrations of TCAs have been reported. More specifically, concomitant use of fluoxetine or paroxetine, both potent CYP2D6 inhibitors, with TCAs was shown to be associated with up to fivefold increase in plasma concentrations of TCAs, and patients undergoing this interaction exhibited toxicity symptoms such as sedation, dry mouth, and urinary retention [Citation91–93]. Fluvoxamine, a potent CYP2C19 inhibitor, caused up to fourfold increases in plasma concentrations of the TCAs amitriptyline, imipramine, and clomipramine and related clinical signs of toxicity [Citation92]. Antipsychotics are another example of drugs that interact with SSRIs as they are metabolised by one or more of the CYP450 enzymes. Clozapine, olanzapine, and risperidone are the antipsychotics with the most frequent reported effects [Citation94,Citation95]. The most frequent adverse effects for sildenafil were headache and nasal congestion [Citation118]. Other forms of PDE5 inhibitors have been used for the treatment of PE.
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The administration tadalafil 20 mg within 36 h before planned sexual intercourse combined with fluoxetine 90 mg once per week for
MeSH terms
Ejaculation retarding by peripheral actions may include modulation of contractile response of vas deferens, seminal vesicles, prostate and urethra, induction of a state of peripheral analgesia, and prolongation of the total duration of erection. Central mechanisms may involve lessening of the central sympathetic output [Citation111]. The on-demand administration of 50–100 mg sildenafil citrate stay hard pills for 1–3 months, in patients with PE complicated by ED, was found to safely and effectively improve erectile function and prolong ejaculation [Citation112]. In addition, sildenafil citrate increased confidence, perception of ejaculatory control, and overall sexual satisfaction, and decreased the refractory time to achieve a second erection after ejaculation in men with PE [Citation113]. It has also been shown that sildenafil combined with behavioural therapy produced more prolongation of the IELT and better male and female satisfaction than behavioural therapy alone in the treatment of patients with PE [Citation114].
Topical Treatments for Premature Ejaculation
On-demand administration of 50 mg sildenafil 1 h before planned sexual activity combined with 10 mg paroxetine daily for 3 weeks and then 20 mg on demand, for 6 months provided significant increases in the ILET and intercourse satisfaction than paroxetine alone in potent patients with PE. However, combined treatment is associated with a mild increase in drug-related side-effects (headache and flushing episodes) [Citation115]. Sildenafil citrate combined with paroxetine and psychological and behavioural counselling alleviated PE in patients in whom other treatments failed [Citation116]. Administration of 50 mg sildenafil on-demand 1 h before planned sexual activity combined with 50 mg sertraline daily, for 12 weeks produced more prolongation of the IELT, and better male and female satisfaction than sertraline alone in patients with PE [Citation117]. Furthermore, the on-demand administration of 50 mg sildenafil citrate 1 h before planned sexual activity for 6 months in patients with PE provided significant increases in the IELT and intercourse satisfaction than 20 mg paroxetine daily and the squeeze technique. 12 weeks in patients with lifelong PE resulted in significant increase in the IELT when compared to fluoxetine or tadalafil alone [Citation51].
How well do pills work against ejaculation too fast?
Fluoxetine and fluvoxamine can interact with anticonvulsants valproate and carbamazepine through their inhibitory effect on CYP2C9 and CYP3A4/5 respectively. Serious reactions including excessive tiredness, irritability, dizziness, and tremor have been reported leading to the discontinuation of the SSRI [Citation96,Citation97]. Serotonin syndrome is a group of symptoms that may occur following the combination of two or more serotonergic medications. It is typically seen when SSRIs are co-administered with lithium, tryptophan and monoamine oxidase inhibitors [Citation98]. The release of serotonin by platelets is important for maintaining haemostasis, thus SSRIs may increase the risk of bleeding.
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Interactions have been reported with anticoagulants such as warfarin and clopidogrel. Based sex tablet for women on their strong inhibition of CYP2C9, fluoxetine and fluvoxamine have the highest potential risk for inhibiting warfarin metabolism thereby causing excessive bleeding. Furthermore, several SSRIs are potent inhibitors to CYP2C19 abolishing the antiplatelet response to clopidogrel [Citation99]. Topical anaesthetics have been used for treatment of PE to decrease penile stimulation, and thus delay the time to ejaculation. The application of lidocaine-prilocaine 5% cream to penis before covering it with a condom 20–30 min before intercourse delayed ejaculation in men with PE.
Efficacy of sertraline in treatment of PE
Prolonged application (30–45 min) before intercourse resulted in loss of erection [Citation100]. Reduction in genital sensitivity of both partners may limit repeated use of topical anaesthetics [Citation101]. Lidocaine-prilocaine cream used for a period of 30–60 days significantly increases the mean IELT, especially when penile hypersensitivity is likely to be the cause. The main side-effects of topical anaesthetic application included retarded ejaculation of >30 min, decreased penile sensitivity, penile irritation, and decreased vaginal sensitivity [Citation102]. Topical anaesthetics are contraindicated for patients and/or their partners with allergies to any component of the product [Citation103]. The on-demand administration of 10 mg vardenafil for 16 weeks provided significant increase of IELT and reduced post-ejaculatory refractory time in men with lifelong PE [Citation119].
- Vardenafil is primarily used for ED, but may impact ejaculation timing.
- Vardenafil can sometimes prolong the time before ejaculation.
- It works by increasing blood flow, possibly affecting ejaculatory control.
- Not approved specifically for premature ejaculation but used off-label.
- Combining Vardenafil with behavioral therapy may improve results.
- Possible side effects include headache, flushing, and nasal congestion.
- Using Vardenafil without medical guidance can be risky.
- It may interact with other medications, altering effectiveness or safety.
- Dose optimization is important to manage side effects and efficacy.
- Vardenafil requires careful timing relative to sexual activity.
- Not a cure for PE but can help some men delay ejaculation.
- Medical consultation is essential before using Vardenafil for PE.
Improvement in confidence, perception of ejaculatory control and overall sexual satisfaction were reported.
| Side Effect | Incidence Rate | Severity | Recommendations |
|---|---|---|---|
| Headache | 15-20% | Mild to moderate | Use hydration and NSAIDs if necessary |
| Flushing | 10-15% | Mild | Typically resolves over hours |
| Dizziness | 5-8% | Mild | Avoid sudden position changes |
| Nasal Congestion | 12% | Mild | Temporary, respond with decongestants |
The use of 5 mg tadalafil once daily plus lidocaine anaesthetic spray in treatment
- Vardenafil's effect duration typically ranges from 4-6 hours.
- It may help improve confidence in men with PE.
- Vardenafil is a PDE5 inhibitor primarily targeting ED.
- Off-label use for PE is common but not officially approved.
- Psychological factors also influence premature ejaculation.
- Combining Vardenafil with topical anesthetics may enhance delay.
- It is contraindicated with nitrate medications.
- Vardenafil does not directly alter ejaculatory reflexes.
- Proper dosage can minimize risks and maximize benefits.
- Sometimes men use Vardenafil with additional pelvic exercises.
- Men should avoid alcohol while using Vardenafil.
- Long-term safety data for PE use is limited.
of lifelong PE was more effective than tadalafil alone or lidocaine anaesthetic spray alone [Citation120].
Tricyclic antidepressants
Administration of 20 mg fluoxetine daily plus local application of lidocaine ointment was found to be more effective than fluoxetine alone [Citation104]. The SS-cream is formed from nine natural substances including ginseng and cinnamon and has local desensitising and vasoactive effects differing from the local anaesthetics in the fact that it persists for up to 2 h. It promises to be an effective and safe therapeutic modality for patients with PE [Citation105]. Applying SS-cream on the glans penis 1 h before planned sexual intercourse, lead to prolongation of ejaculatory latency time and improvement of sexual satisfaction for both partners with no adverse effect [Citation105,Citation106]. A study assessed penile vibratory threshold change using a bio-thesiometer using various doses of SS-cream and found that SS-cream increased the penile sensory threshold in a dose-dependent manner [Citation107].
Management of premature ejaculation: a clinical guideline from the Italian Society of Andrology and Sexual Medicine (SIAMS)
Topical eutectic mixture for PE (TEMPE or PSD502) is a formulation of lidocaine and prilocaine in a metered dose aerosol-delivery system. Each spray delivers 7.5 mg lidocaine and 2.5 mg prilocaine. It is fast acting (within 5 min) and appears to be effective in improving the IELT and sexual satisfaction in patients with PE. It does not penetrate keratinised epithelium, and so only anaesthetises the glans, with no systemic side-effects and a low incidence of local side-effects [Citation108,Citation109]. Dyclonine is a local anaesthetic usually used in the field of dentistry.
Authors and Affiliations
It has been combined with the vasodilator alprostadil and used to treat PE. The product is applied 5–20 min before intercourse to the tip of the penis in the region of the meatus. One pilot study claimed positive results with it; however, the data were limited and further studies are warranted before conclusions can be made [Citation110]. Several clinical trials have examined the potential effectiveness of the PDE5 inhibitor, sildenafil, in the treatment of PE. The rationale for the use of PDE5 inhibitors in the treatment of PE may be due to peripheral and/or central mechanisms.