Progress In The Application Of Antidepressants In The Treatment Of Chronic Pruritus

Itching is a kind of skin discomfort that causes the desire to grab, and it is chronic itching for more than 6 weeks. The survey shows that the lifetime prevalence of chronic itching is as high as 22%, and the impact can be comparable to chronic pain. As the most common symptom of dermatology, chronic pruritus is found in various skin diseases such as eczema, chronic urticaria, psoriasis, atopic dermatitis, etc. It is also found in systemic diseases such as advanced chronic kidney disease, cholestasis, polycythemia, lymphoma, etc. In addition to diseases, neurological factors can also cause chronic itching. At present, the treatment of chronic pruritus is mainly divided into two aspects: local treatment and systemic treatment. The former has many external coolants, corticosteroids, capsaicin, etc., the latter commonly used antihistamines, opioid receptor antagonists, immunosuppressive agents, calcium agents and the like. In addition, physical therapy such as phototherapy, starch bath and traditional Chinese medicine are also commonly used to treat chronic itching. However, a considerable number of patients have poor efficacy in routine antipruritic treatment, especially the complicated and even unclear refractory itching and the itching associated with systemic diseases.
Progress in the application of antidepressants in the treatment of chronic pruritus

1.Depressive mood and chronic itching

Emotional disorders can aggravate itching, and itching often does not make the patient’s mood worse, forming a vicious circle of illness. Depression is common in a variety of skin diseases such as chronic simple moss, psoriasis, chronic urticaria, and atopic dermatitis. The itching discomfort directly drives the patient to scratch and stimulate the skin, resulting in a pleasant and comfortable feeling. In normal people, scratching behavior can relieve itching to some extent, but it can not be relieved in patients with chronic itching. For example, in patients with atopic dermatitis, it is not possible to relieve itching, whether it is scratching the lesion or non-lesional lesions, and it is actually an increase in itching. The vicious circle of “itching – scratching – itching is aggravating” is an important cause of chronic itching, and depression can drive scratching behavior. Antidepressants can improve the depression of patients, and also help to inhibit scratching and interrupt the “itching – scratching – itching” cycle. It is speculated that inhibition of scratching may be a target for the treatment of chronic pruritus by antidepressants.

2. Antidepressants treat chronic itching

Among the antidepressants used to treat chronic pruritus are tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), norepinephrine and specific serotoninergic antidepressants. (NaSSA), it is associated with various skin diseases such as chronic urticaria, localized neurodermatitis, atopic dermatitis and chronic simple moss, as well as pruritus associated with systemic diseases such as chronic renal failure and primary biliary cirrhosis.

2. 1 Tricyclic antidepressant (TCA)

Tricyclic antidepressants are non-selective monoamine uptake inhibitors that exert antidepressant effects by inhibiting the reuptake of norepinephrine (NE) and serotonin (5-HT) to increase synaptic interstitial concentrations. It has the effect of blocking the α1 adrenergic receptor and the H1 receptor.

2.1.1 Amitriptyline

Amitriptyline is used in the treatment of itching. For example, 2% amitriptyline and 0.5% ketamine compound gel can be used to treat severe itching after herpes zoster. It is also effective for refractory chronic itching amitriptyline of unknown cause. Poterucha et al reported that patients with severe pruritus for 5 years had 1% to 3 times a day using 1% amitriptyline hydrochloride and 0.5% ketamine hydrochloride cream, and the itching was significantly relieved.
In addition to the route of exclusion, oral amitriptyline can also treat itching. Such as mossy amyloidosis stubborn itching, oral antihistamines and topical hormones and other conventional antipruritic treatment is ineffective. Oral administration of amitriptyline, starting dose of 10mg per night, according to the patient’s treatment response gradually increased to 25mg, after the condition is stable, 10mg maintenance, long-term follow-up confirmed that itching is effectively controlled. Because amitriptyline is mainly metabolized by the liver, it has a small burden on the kidneys, especially for patients with impaired renal function. Yong et al used amitriptyline to treat 2 patients with pruritus of chronic renal failure. Oral amitriptyline 25 mg and 10 mg were given every night, and the pruritus scores decreased significantly within 2 to 3 weeks.

2.1.2 Doxepin

Doxepin has a good anti-H1 receptor effect, can also inhibit acetylcholine, substance P, etc., and alleviate local inflammation. It is used for refractory pruritus with less side effects than immunomodulators, and is very cheap compared with biological agents. unique advantage. In 2014, the American Society of Allergy, Asthma and Immunology guidelines for the diagnosis and management of acute and chronic urticaria were recommended. For the more refractory chronic urticaria, doxepin treatment can be used before using immunomodulators. For the itching associated with systemic diseases, Doxepin also has an ideal therapeutic effect. Lu Geping randomly divided 56 patients with uremia and pruritus into 28 patients in the control group and the experimental group. All patients discontinued antipruritic drugs for at least 7 days before treatment. The experimental group was given Doxepin 25 mg twice daily, and the control group was given a placebo. The skin itching score was recorded separately for 7 days. The results showed that the treatment group was significantly more effective than the control group. According to this, a small dose of oral Doxepin can effectively alleviate the symptoms of uremia and pruritus. Pourrezagholi et al believe that a small dose of doxepin for uremia skin itching can also achieve a good antipruritic effect. In clinical practice, the patient is given 10 mg orally twice a day, twice a day, and the effect is seen after taking the drug for 1 week.

2.2 Selective serotonin reuptake inhibitor (SSRI) SSRI

Antidepressants are highly selective for 5-HT, but have little effect on other transmitters, no obvious orthostatic hypotension, cognitive impairment, anticholinergic and cardiovascular side effects, and are a new class of applications. Antidepressants.

2.2.1 Sertraline

Sertraline is commonly used in the treatment of depression and obsessive-compulsive disorder. The initial dose is 50 mg per day and the maximum dose is 200 mg per day. Clinical studies have found that sertraline can be used to treat chronic itching caused by systemic diseases such as renal pruritus and biliary pruritus. Shakiba et al., hemodialysis end-stage renal disease patients with sertraline 50mg, 1 time / d orally, treatment for 4 months, a summary analysis showed that sertraline treatment effect was significant. Chan et al. treated sertraline with renal-induced pruritus associated with uremia, starting at 25 mg daily for oral administration, followed by a maximum dose of 200 mg, if necessary, in 25 mg increments according to clinical response. The results showed that sertraline can effectively relieve renal pruritus and exert its efficacy at lower doses. In addition, sertraline can also be used to treat pruritus in patients with primary biliary cirrhosis. Wu Xin et al. give sertraline 50 mg daily for 2 weeks, and clinical trials have a certain effect on such pruritus. It is well tolerated, and only one patient has mild sleepiness during treatment, but does not affect daily life. It is suggested that the skin pruritus of primary biliary cirrhosis may be considered oral sertraline in the case of other poor therapeutic effects.

2.2.2 Paroxetine

Paroxetine, as a clinical first-line medication for depression, is also used to treat refractory itching caused by malignant diseases such as advanced tumors. Animal experiments have shown that oral administration of paroxetine can inhibit the aggravation of atopic dermatitis-like dermatitis in NC/Nga mice and reduce scratching behavior. It is speculated that paroxetine may be suitable for clinical use, especially in people with mood disorders. The relevance of paroxetine in patients with atopic dermatitis supports this conclusion. Unotoro et al used paroxetine for biliary stasis pruritus in patients with advanced digestive system tumors. Oral administration of 10 mg can effectively inhibit itching. The duration of efficacy can vary from several hours to 2 days, and has good application prospects. A large proportion of cases of refractory pruritus cannot be diagnosed with physical abnormalities, and may be considered as psychogenic itching, especially for antidepressant treatment. Heisig et al reported a case of paroxetine in the treatment of psychogenic pruritus, the patient was an elderly male, mild dementia, long-term itching symptoms, anti-histamine treatment is ineffective, visible skin lesions left after scratching, no significant laboratory tests found Abnormal, to meet the diagnostic criteria for psychogenic itching. The itching was improved after paroxetine, and the scratching behavior and the resulting skin lesions were significantly reduced.

2.2.3 Escitalopram

The report of escitalopram in the treatment of chronic pruritus is mainly focused on psoriasis. D’Erme et al reported that after six months of treatment with escitalopram in patients with moderate to severe psoriasis, the psoriasis severity index and visual analogue scale, the Hamilton Depression Scale, and the Hamilton Anxiety Scale scores were significantly reduced, and the degree of itching and Emotional disorders have improved. In addition to inhibiting itching itself, escitalopram can also alleviate anxiety, reduce the patient’s scratching behavior, break the vicious circle between itching and scratching, and help relieve itching.

2.2.4 Fluvoxamine

Stnder et al used fluvoxamine and paroxetine in the same SSRI class for the treatment of chronic pruritus, with the best effect of chronic pruritus caused by lymphoma and solid cancer. The effective dose is less than the recommended daily dose of 100 to 200 mg used in the treatment of depression. The specific treatment plan is as follows: 10mg paroxetine or 25mg fluvoxamine as the starting dose, medication for 3d, then gradually increased according to clinical effects, the maximum dose is 60mg and 150mg, the maintenance dose is paroxetine 20mg or fluvoxamine 50mg .
2.3NE and specific 5-HT antidepressant (NaSSA)
NaSSA antidepressants work similarly to TCAs and are dual-channel drugs, but the selectivity is higher than TCAs, which reduces the adverse reactions and better tolerance while ensuring efficacy. Mirtazapine exerts anti-depressant effects through 5-HT and NE energy effects through secondary mechanisms. Recently, several clinical reports of mirtazapine have been used for malignant tumors with stubborn itching, which can significantly relieve symptoms and are not effective for conventional treatment. The refractory itching has important reference value. TNishi et al reported a case of a 56-year-old female patient with peritoneal metastasis of pancreatic head cancer. The total bilirubin was as high as 9.9 mg/dl, systemic stubborn itching, antihistamine treatment was ineffective, and itching was relieved on the second day of oral mirtazapine. . Araki et al reported that an elderly patient with persistent pruritus in advanced lymphoma received oral mirtazapine 15 mg daily. After 7 days, the pruritus improved significantly, and the oral symptoms disappeared. Lee et al reported a case of advanced refractory pruritus in patients with advanced breast cancer. Oral administration of pregabalin and hydroxyzine had little effect. Add 7.5mg of mirtazapine once a night, improve itching after 12h, increase the dose to 15mg after 48h, the subjective evaluation of pruritus decreased from “200+” to “2”, followed up for 1 month, no recurrence.

3. Conclusion

The current mechanism of antidepressant treatment of chronic pruritus remains to be further studied, but for patients with refractory chronic itching, especially those with severe mood disorders or depression at the same time, the application of the above antidepressants can be double Benefits, and can reduce the accumulation of side effects of drugs, reduce the burden of medication for patients, and facilitate individualized treatment. Serious systemic diseases such as chronic kidney disease, malignant tumors and other itching, anti-depressants often have unexpected effects when common antipruritic drugs fail to achieve satisfactory results, or when organ damage is limited by the use of antipruritic drugs. For palliative care patients, antidepressants can not only relieve itching but also alleviate negative emotions and improve quality of life. With the shift from the medical research model to the bio-psycho-social model, we expect more psychosocial treatments, such as behavioral cognitive therapy, behavioral habit change training, etc., to apply to the treatment of chronic itching, to provide more diverse patients. Personalized, personalized choices.