Newest medicine for depression


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  • SAMHSA’s National Helpline is a free, confidential, 24/7, 365-day-a-year treatment referral and information service (in English and Spanish) for individuals and families facing mental and/or substance use disorders.

    Also visit the online treatment locator.

SAMHSA’s National Helpline, 1-800-662-HELP (4357) (also known as the Treatment Referral Routing Service), or TTY: 1-800-487-4889 is a confidential, free, 24-hour-a-day, 365-day-a-year, information service, in English and Spanish, for individuals and family members facing mental and/or substance use disorders. This service provides referrals to local treatment facilities, support groups, and community-based organizations.

Also visit the online treatment locator, or send your zip code via text message: 435748 (HELP4U) to find help near you. Read more about the HELP4U text messaging service.

The service is open 24/7, 365 days a year.

English and Spanish are available if you select the option to speak with a national representative. Currently, the 435748 (HELP4U) text messaging service is only available in English.

In 2020, the Helpline received 833,598 calls. This is a 27 percent increase from 2019, when the Helpline received a total of 656,953 calls for the year.

The referral service is free of charge. If you have no insurance or are underinsured, we will refer you to your state office, which is responsible for state-funded treatment programs. In addition, we can often refer you to facilities that charge on a sliding fee scale or accept Medicare or Medicaid. If you have health insurance, you are encouraged to contact your insurer for a list of participating health care providers and facilities.

The service is confidential. We will not ask you for any personal information. We may ask for your zip code or other pertinent geographic information in order to track calls being routed to other offices or to accurately identify the local resources appropriate to your needs.

No, we do not provide counseling. Trained information specialists answer calls, transfer callers to state services or other appropriate intake centers in their states, and connect them with local assistance and support.

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    Assures teens with parents who abuse alcohol or drugs that, "It's not your fault!" and that they are not alone. Encourages teens to seek emotional support from other adults, school counselors, and youth support groups such as Alateen, and provides a resource list.

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Last Updated: 08/30/2022

SAMHSA Behavioral Health Treatment Services Locator

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Welcome to the Behavioral Health Treatment Services Locator, a confidential and anonymous source of information for persons seeking treatment facilities in the United States or U.S. Territories for substance use/addiction and/or mental health problems.

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The Locator is authorized by the 21st Century Cures Act (Public Law 114-255, Section 9006; 42 U.S.C. 290bb-36d). SAMHSA endeavors to keep the Locator current. All information in the Locator is updated annually from facility responses to SAMHSA’s National Substance Use and Mental Health Services Survey (N-SUMHSS). New facilities that have completed an abbreviated survey and met all the qualifications are added monthly. Updates to facility names, addresses, telephone numbers, and services are made weekly for facilities informing SAMHSA of changes. Facilities may request additions or changes to their information by sending an e-mail to [email protected], by calling the BHSIS Project Office at 1-833-888-1553 (Mon-Fri 8-6 ET), or by electronic form submission using the Locator online application form (intended for additions of new facilities).

Avelity: A New Antidepressant for the Most Severe Depressions

Main

Avelity (Auvelity, dextromethorphan + bupropion, 45mg/105mg) is a new oral drug for the treatment of major depressive disorder in adults.

Unlike all existing oral antidepressants, Aveliti, also known under the code name AXS-05, is characterized by a rapid and long-lasting therapeutic effect. Improvement of depressive symptoms is noted literally in a week, remission occurs in two. "Avelity" is able to successfully cope with the symptoms of even a severe form of depression in most patients.

The medical need for new antidepressants that are effective and safe is extremely high due to the continuing increase in the prevalence of depression worldwide.

Thus, in the US alone in 2020, there were 21 million adults who had experienced at least one episode of major depressive disorder in the previous year. Between March and April 2021, an estimated 85 million American adults are experiencing major depressive symptoms, driven in large part by the ongoing COVID-19 pandemic..

Avility was developed by Axsome Therapeutics.

The U.S. Food and Drug Administration (FDA) approved Avility in mid-August 2022.

"Aveliti" will go on sale at the beginning of the fourth quarter of 2022.

The price of "Aveliti" will be determined in the coming weeks.

Aksam is looking for a commercial partner to bring the drug to the market outside the US.

The American regulator had to decide on the approval of "Aveliti" at the end of August 2021. However, the FDA requested additional data from Aksam to resolve the incompleteness of the registration dossier related to analytical methods in the section "Chemical properties, production process and quality control". At that time, the stock quotes of the company lost almost 40%, later winning back the fall, although not in full.

Axam intends to expand the range of indications for Avality by proving its applicability in the treatment of agitation in Alzheimer's disease and as an adjunct in the treatment of nicotine dependence for those who want to quit smoking.

What is Major Depressive Disorder? symptoms. In severe cases, the patient may resort to suicide. [12]

Depression is a worldwide disease and one of the leading causes of disability. Depression affects approximately 3.8% of the world's population, and about 280 million people suffer from it. In low- and middle-income countries, the problem of depression is particularly acute: factors such as lack of resources, lack of trained health workers, and social stigma associated with mental disorders pose obstacles to the effective treatment of depression. It is not uncommon for people with depression to be misdiagnosed in countries of all income levels. [3]

Major depressive disorder is difficult to treat: nearly two-thirds of patients do not adequately respond to existing first-line oral antidepressants. Most initial treatment failures also end in the failure of all subsequent lines of therapy. [four]

Patients with clinical depression are diagnosed with treatment-resistant depression if they do not respond to two or more lines of antidepressant therapy of different pharmacological groups.

Currently approved oral antidepressants act predominantly through monoaminergic mechanisms. Since achieving a clinically significant response requires a long time of their continuous use (up to 6-8 weeks), and the therapy itself is accompanied by adverse events, this seriously affects the adherence of patients to treatment: they often stop therapy prematurely. [4] [5] [6]

That is why there is a high unmet medical need for fundamentally new pharmacotherapeutic options for the treatment of clinical depression: such drugs must be well tolerated, act quickly, and provide a stable clinical effect. [7]

Avelity: the combined mechanism of action of dextromethorphan with bupropion

The oral combination drug Avelity (Auvelity, dextromethorphan + bupropion, 45 mg/105 mg), codenamed AXS-05, is an N-receptor antagonist methyl-D-aspartate (NMDA) with multimodal activity.

Dextromethorphan, being a noncompetitive NMDA receptor antagonist, also works as a sigma-1 receptor agonist and an inhibitor of serotonin and norepinephrine transport proteins.

Antagonism of the NMDA receptor, which is an ionotropic glutamate receptor, causes an antidepressant effect realized by modulation of glutamate neurotransmission due to changes in the inhibitory tone of interneurons and/or a direct effect on the postsynaptic NMDA receptor. Sigma-1 receptor agonism modulates glutamate and monoamine signaling. [one]

NMDA receptor antagonism with ketamine is well known to produce a rapid and significant antidepressant effect. [2] However, the use of ketamine is accompanied by a number of difficulties, including parenteral administration, potential for abuse, psychotomimetic side effects, and a narrow therapeutic window. However, March 2019Janssen, part of Johnson & Johnson, succeeded in bringing Spravato (esketamine) nasal spray to the market for treatment-resistant depression and then adding a treatment in August 2020 major depressive disorder with acute suicidal ideation and behavior. Esketamine is the S(+) enantiomer of ketamine.

The similarity between dextromethorphan and ketamine in terms of receptor pharmacology and pharmacodynamic effects suggests that dextromethorphan has antidepressant efficacy without the limitations of ketamine. However, whether the antidepressant effect is due to NMDA receptor antagonism is still unclear. [3] [4]

Bupropion serves as a bioavailability booster for dextromethorphan, which is metabolized too rapidly in the human body to achieve plasma concentrations necessary to achieve desired psychotherapeutic effects.

Since bupropion inhibits cytochrome P450 2D6 (CYP2D6) and dextromethorphan is a substrate for this enzyme, the CYP2D6-mediated metabolism of dextromethorphan is suppressed, which is reflected by an increase in its plasma level and an extension of the half-life. Thus, the antidepressant effect is endowed with a stable character. [5]

Bupropion is a dual norepinephrine and dopamine reuptake inhibitor. [6]

In addition, dextromethorphan and bupropion are nicotinic acetylcholine receptor antagonists.

The complex antidepressant mechanism of action of "Aveliti" is tied to a number of signaling cascades related to synaptic plasticity, and is provided by strengthening synaptic connections and improving communication interactions between brain cells. The drug increases brain levels of serotonin, norepinephrine and dopamine, which are key neurotransmitters involved in mood regulation.

"Aveliti" also has anti-inflammatory properties. [7] [8] [9] [10] [11] There is an association between depression and inflammation: patients with depression have elevated serum levels of interleukin 6 (IL-6), interleukin 1 (IL-1), C-reactive protein (CRP), tumor necrosis factor (TNF) and other inflammatory biomarkers. [12] [13] [14] [15] [16]

Avality: efficacy and safety in the treatment of major depressive disorder

Main study

The GEMINI (NCT04019704) phase III clinical trial (randomized, double-blind, placebo-controlled, multicentre) enrolled adult patients (n=327) with moderate-severe (total MADRS score ≥ 25) major depressive disorder.

Baseline characteristics of the subjects: average age 42 years, women 66%, average total MADRS score is 33.

Mosmedpreparaty

Patients were given placebo or dextromethorphan plus buprion twice daily for 6 weeks; participants received only one dose for the first three days.

The primary endpoint of treatment efficacy was stated as change in total score on the Montgomery-Osberg Depression Rating Scale (MADRS) [higher score = more severely depressed] after 6 weeks.

The Avelity group showed a decrease in the total MADRS score by 16.6 points on average versus 11.9 points in the placebo group (p=0.002).

Those who received dextromethorphan plus buprion showed a statistically significant (p=0.007) difference with the control group already at the 1st week of treatment: the total MADRS score decreased by an average of 7.3 points - against 4.9item.

The use of "Aveliti" provided access to clinical remission (no clinically significant symptoms of depression and an overall MADRS score ≤ 10) after 2, 3, 4 and 6 weeks of therapy in 17%, 24%, 32% and 40% of patients versus 8%, 11%, 12% and 17% in the placebo group (p=0. 013, p=0.002, p<0.001, p<0.001).

Avality resulted in an early and sustained clinical response (≥ 50% reduction in total MADRS score) after 1, 2, 3, 4 and 6 weeks of treatment in 15%, 28%, 42%, 49% and 54% of patients versus 7%, 17%, 25%, 27% and 34% in the placebo group (p=0.035, p=0.020, p=0.001, p<0.001, p<0.001).

The combination of dextromethorphan and buprion had a statistically significant effect on improvement scores on the Global Clinical Impression of Improvement (CGI-I), Global Clinical Impression of Disease Severity (CGI-S), Patient Global Impression of Improvement (PGI) -I), on the Short Questionnaire of Satisfaction with Quality of Life (Q-LES-Q-SF), on the Rapid Self-Questionnaire for Depressive Symptoms (QIDS-SR-16).

The safety profile of "Avelity" was characterized by acceptable tolerability. Among the most common adverse events that occurred during treatment: dizziness (in 16% of patients in the Avility group vs. 6% in the placebo group), nausea (13% vs. 9%), headache (8% vs. 4%), diarrhea (7% vs 3%), drowsiness (7% vs 3%), dry mouth (6% vs 2%). All adverse reactions were mild to moderate in severity.

The Avelity Prescribing Information contains a black box warning about an increased risk of suicidal thoughts and behavior in children, adolescents and young adults (18–24 years) taking antidepressants. This patient population should be carefully monitored for clinical deterioration and suicidal tendencies. Avality is not approved for use in pediatric patients.

Longitudinal Study #1

The COMET (NCT04039022) phase III (non-randomized, open label, multicenter) clinical trial enrolled adult patients (n=611) with moderate to severe (MADRS overall score ≥ 25) major depressive disorder.

Baseline characteristics of subjects: mean age 42, female 62%, mean total MADRS score of 33.

For 12 months, patients were administered twice daily dextromethorphan with buprion.

Long-term treatment of major depressive disorder with the drug "Aveliti" made it possible to achieve the following indicators of the effectiveness of therapy.

Mean reductions in total MADRS score were 9.1, 14.0, and 21.1 points at 1, 2, and 6 weeks. After 6 and 12 months this score decreased by 23.9 points and 23.0 points .

19%, 40%, and 73% of patients were clinically responding to treatment for depression after 1, 2, and 6 weeks of therapy. Clinical response was fair for 85% and 83% of subjects after 6 and 12 months of treatment.

Clinical remission of depression was recorded for 8%, 22% and 53% of patients after 1, 2 and 6 weeks of treatment. This status was reached by 69% and 69% of participants after 6 and 12 months of therapy.

Clear improvements in depressive symptoms, as assessed by the CGI-I scale, were noted in 27%, 50% and 83% of patients after 1, 2 and 6 weeks of treatment. The same is registered for 87% and 93% of patients after 6 and 12 months of therapy.

Clinical response to treatment for depression on the Sheehan Disability Scale (SDS; total score ≤ 12) assessing functionality at work/school, social life, family life/home responsibilities, documented for 42.9%, 55.1% and 70.7% of patients after 1, 2 and 6 weeks of treatment. This was true for 81% and 76% of subjects after 6 and 12 months of therapy.

The safety profile of "Avelity" was characterized by acceptable tolerability. Among the most common adverse events that occurred during treatment were dizziness (in 13% of patients), nausea (12%), headache (9%), dry mouth (7%), loss of appetite (6%). All adverse reactions were mild to moderate in severity.

Longitudinal study #2

The EVOLVE (non-randomised, open-label, multicentre) clinical trial enrolled adult patients (n=186) with moderate to severe (MADRS ≥ 25 total score) major depressive disorder who were previously treated with at least one antidepressant during the current episode of depression and whose treatment has not justified itself.

Baseline characteristics of the subjects: the average total MADRS score was 32.

Patients were administered twice daily dextromethorphan with buprion for up to 15 months.

Appointment of "Aveliti" led to a rapid improvement in depressive symptoms. So, the average decrease in the total MADRS score was 9.1±7.6 (p<0.001), 13.3±8.6 (p<0.001) and 20.4±7.8 (p<0.001) after 1, 2 and 6 weeks respectively. At the same time, a clinical response was recorded for 17.7%, 39.0% and 74.2% of patients. 9 went into remission of major depressive disorder0085 5.7%, 16.2% and 46.0% of subjects .

The antidepressant effect of "Aveliti" was characterized by long-term and stability throughout the 12 months of therapy. Thus, the remission status was fair for 65% and 68% of patients after 6 and 12 months of treatment.

Functional remission of major depressive disorder, according to the SDS scale (total score ≤ 6), was achieved in 18%, 31% and 40% of patients after 1, 2 and 6 weeks of treatment. After 6 and 12 months of therapy, 54% and 59% of subjects .

Avality provided relief from anxiety, as measured by the Hamilton Anxiety Scale (HAM-A), in 36%, 51%, and 58% of patients who achieved remission for this clinical indicator (total score ≤ 7) after 1 , 2 and 6 weeks of treatment. Remission after 6 and 12 months of therapy was recorded for 75% and 78% of subjects .

Long-term administration of "Aveliti" was characterized by acceptable tolerability. Among the most common adverse events were: nausea (in 8.9% of patients), headache (7.5%), dry mouth (6.2%), insomnia (5.5%), dizziness (5.5%).

Complementary study

The ASCEND (NCT03595579) phase II clinical trial (randomized, double-blind, active control, multicenter) enrolled adult patients (n=80) with moderate-severe (total MADRS score ≥ 25) major depressive disorder. disorder.

Baseline characteristics of subjects: mean age 37. 5 years, women 64%, mean total MADRS score is 32.

Mosmedpreparaty

Participants were given either dextromethorphan with bupropion or bupropion alone, twice daily for 6 weeks.

The use of "Aveliti" provided a statistically significant decrease in the total MADRS score: for the entire course of treatment, its decrease was an average of 13.7 points - against 8.8 points in the bupropion group (p<0.001).

At weeks 1, 2, and 6, patients treated with dextromethorphan with bupropion showed a reduction in total MADRS score of 7.4, 12.5, and 17.3 points vs. 4.5, 7.8 and 12.1 points in the control group (p=0.169, p=0.024, p=0.013).

Clinical remission was recorded at week 6 in 47% of subjects in the dextromethorphan plus bupropion group versus 16% in the control group (p=0.004).

Appointment "Aveliti" led to an improvement in other indicators of the effectiveness of the treatment of depression, including scores on the MADRS-6 subscale (major symptoms of depression), on the CGI-I scale, on the CGI-S scale.

Avility's safety profile was acceptable. There were no side effects associated with psychotomimetic disorders, weight gain, increased sexual dysfunction.

Aveliti: Market Prospects

Major depressive disorder killed many experimental drugs. This disease is very difficult to treat, and therefore it is surprising how dextrometrophan with bupropion managed to easily pass three clinical trials important for regulatory approval. Moreover, the therapeutic efficacy of "Aveliti" was consistent in all three studies, which is almost impossible to achieve in the case of almost any mental disorder. The well-known problem of drug testing in neuropsychiatric disorders, when in one clinical trial an experimental drug works with due efficiency, while in another, even if completely similar in design, it fails.

Thus, Avelity, validated in the phase III pivotal GEMINI (NCT04019704), phase III long-term COMET (NCT04039022) and phase II supplementary ASCEND (NCT03595579) clinical trial, demonstrated a reduction in total MADRS score of 16. 6, 21.1 and 17.3 points after 6 weeks of treatment, or, as a percentage of baseline, by 50%, 64%, 54%. 40%, 53% and 47% of patients went into clinical remission of depression, respectively. And all this without any negative effects.

Long-term use of dextrometrofan with bupropion improved the proportion of patients reaching clinical remission status to 69% for six months of treatment. And again, no negative side effects.

Aksam would like to reinforce confidence in the therapeutic viability of Avelity by proving that it also successfully copes with therapeutically resistant depression (when two or more lines of therapy with different standard antidepressants do not help), but it did not turn out very smoothly. The Phase III STRIDE-1 (NCT02741791) clinical trial comparing the drug to bupropion failed to demonstrate a statistically significant overweight of the experimental drug. The problem was not with Aveliti itself, but with study design flaws that led to insufficient statistical power. Subsequent MERIT (NCT04608396) phase II confirmed that "Avelity" is capable of delaying the onset and preventing the recurrence of depressive symptoms. The COMET-TRD cohort in COMET (NCT04039022) also showed adequate efficacy. However, Axam is not currently considering dextrometrofan with bupropion as a drug for treatment-resistant depression.

Axam is convinced that Avility is suitable for the treatment of other clinically relevant patient groups: major depressive disorder not responding to one line of standard antidepressant therapy and major depressive disorder with suicidal tendencies. Corresponding COMET-AU and COMET-SI cohorts in COMET (NCT04039022) this was confirmed: after 6 weeks of treatment, remission was registered in 40% and 50% of patients; suicidal tendencies disappeared in 60% of patients already in the first week of therapy.

At the same time, Axam continues to test Aveliti in the treatment of agitation in Alzheimer's disease and the treatment of nicotine addiction. For example, in the phase II/III ADVANCE (NCT03226522) clinical trial, baseline total scores on the Cohen-Mansfield Excitability Assessment Inventory (CMAI) decreased by almost half, and in the phase II clinical trial NCT03471767, dextromethorphan with bupropion provided a greater reduction in the number of cigarettes smoked and a greater reduction smoking intensity versus bupropion alone, an approved drug for quit smokers.

Industry observers estimate that Aveliti will cross the threshold of half a billion dollars in annual sales only by 2026. Such restrained forecasts are obviously due to delays in the regulatory verdict. Obviously, once the drug is approved, financial expectations will improve dramatically. What can I say if, before the regulatory problems, the sales forecast for Avility was extremely optimistic: in 2026, the drug sales should have reached the level of 1.3 billion dollars a year.

In terms of intellectual property protection, Aveliti is doing well: the proprietary combination of dextromethorphan with buprion is securely patented until 2037–2040.

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Fighting depression 10 modern drugs

Depression is a real problem, and the number of doctors is growing year by year. Contact psychosomatic medicine and solve it by taking antidepressants. These are drugs that regulate the production of hormones and biochemical processes in the body. It is strictly forbidden to prescribe yourself because it is a complex drug and has certain limitations and side effects. Physicians must authorize bookings and manage appointments. Here are some of the most effective and most common, how many advantages and disadvantages.

What is meant by depression

Doctors knew from ancient Greece and Egypt. Hipocrates describes restlessness, despair, insomnia, anorexia, and frustration as "melancholy". In many cases trauma in childhood and intense frequent stress since they become adults. There are various factors such as the death of an important person, deterioration of the living environment, alcoholism and brain disease. Such cases are called psychogenic depression.

The second type is internal. The problem is not a big shock from the outside, but from an internal cause. People are always dissatisfied with themselves and are criticized. Many patients experience a panic attack associated with fear and anxiety.

How long does a depressed period last?

Many people confuse normal mood depression with depression. If this state does not last long and is immediately restored, it is not a state of depression. Symptoms continue for several months, and when a person's life has changed dramatically, the problem becomes clear. Then you should see a doctor.

What happens to the body

The most common theory is that the neurotransmitters in the brain are malfunctioning. These substances transmit signals from neurons to neurons, affecting the human mood. Functional impairments cause this decrease in transmission rate and decrease in the irotransmitter itself. Serotonin, called the happy hormone, is the most affected. To make it easier to understand, this biochemical process can be compared to the drop in blood sugar in diabetes.

How depression is treated

There have been various treatments for depression. In ancient times a-vomiting and laxatives. In the Renaissance, wine and sunbathing. Age of Enlightenment - External stimuli, such as insects. In the 19th century, a piece of camphor was dissolved in tabular acid. At present, medicines that are prohibited from being sold and those that are recognized as medicines have been used for treatment.

Obviously, these drugs did not affect the increase in serotonin. And treatment only normalizes its production. This is after a modern antidepressant that has few side effects and does not become safe and becomes dependent on the body. It is a drug that targets a precise balance of a neurotransmitter such as serotonin, noruepinfrin, and dopamine.

Prescription

Even a healthy person takes an antidepressant, it will not be effective. For patients with depression, acceptance can be effective.

  • Improve psychological status.
  • Eliminate disappointment
  • Increased mental and physical activity
  • overcome sadness

Psychiatrists prescribe ant and depid agents for chronic back pain and headaches. Also, even if the painkillers are not produced in the body, such as irritable bowel syndrome and incontinence. Drug therapy helps restore the mechanism that suppresses pain.

These products can only be consumed according to a doctor's prescription because it is a strong incentive. Independent goals are expensive o-conditions can get worse. Only doctors calculate the amount of medicine to be taken per day. It is necessary to consult with a psychotherapist in parallel with the treatment of psychiatrists and neurologists.

Precautions

  • Start your prescribed medicine at a low dose and take 1/4 tablet for the first two days. Gradually increase and use the normal amount. Thus, the body adapts better. Not enough to complete the course.
  • The first effect appears only two weeks after the start of hospitalization. Sustained effect-After six months, you need to continue taking the medication without interruption, without rest.

Remedies do not combine with Melatonin, St. Jung's Stars, Remedies, Cybbtramin and 5-ADR. These combinations can increase serotonin to dangerous levels. It should not be used in combination with monoamine oxidate inhibitors such as Cypralex. When writing a prescription, the doctor considers these points.

The best antidepressants

In 2017, an international team of scientists conducted a large-scale study on the effects of modern antidepressants. In the medical world, some drugs have long been claimed to be given only as a placebo. The goal is to find out what is the most efficient and active. The project monitored 116,000 patients, resulting in the authoritative Lancet journals. We provide.

1. Latin Island

This medicine is a new generation. Ectylatine is used for severe depression and severe anxiety. Promotes the release of dopamine and noruepinephrine and stimulates melatonin receptors. The standard treatment is e-25-50 mg 1 hour/day. It helps to restore the normal structure of sleep and eliminate anxiety and panic attacks.

+ Does not adversely affect attention or memory.

+ Do not suppress during the day.

+ No sexual deviation.

There is no relationship with blood pressure.

+Don't lose weight as soon as you stop taking it.

In case e-1-10% sweating, diarrhea and constipation increased.

-It may increase fatigue and drowsiness.

-There is no evidence-based review for the safety of patients with renal and hepatic dysfunction, therefore it is recommended that these patients should avoid taking medicines containing the active substances agoline. Increase.

2. Amitripsis

Pe l-Antidepressant. Among the groups, amitripine is said to be the most reliable in the World Health Organization. Standard doses are 200-250 mg/day. Its effect is to suppress the reverse side of neurotransmitters. A good remedy for severe endogenous disorders. In addition, it contains sedative and hypnosis. It is effective in the treatment of neuropathic pain and the prevention of migraine.

+ Products containing amitripline are inexpensive.

+ High reliability, few side effects.

+ It is relatively safe even when breastfeeding.

- There is a possibility of visual dysfunction and dry mouth side effects.

- High blood pressure

- Patients are constipated.

3. ESSITARO SLUMA

This is a staggering, belonging to the group of modern drugs that delay the reversal of serotonin (SIOS). Most often it is recommended to shoot with anxiety and panic attacks. Take 10mg per day once, once. Escitalopram is effective and indicated for patients who are contraindicated for the use of the triple county drugs.

+ Long-term effects occur after 3 months.

+ It is adapted to patients with cardiovascular diseases.

- Abnormal function of the gastrointestinal tract in each patient, which is most pronounced as diarrhea.

-B, during the first two weeks it is recommended to start treatment with a low dose and gradually increase.

-Mated pregnancy and breastfeeding are contraindicated.

4. Mirta Zapin

Tetra-a-cycline based on the drug. Mirazapine is an anxiety-suppressing stimulant with a mild sedative effect. The average amount is 30 mg/day, after use. It is usually given to patients who have lost interest in life and no longer feel joy or pleasure. Effective for sleep, especially for early growth.

+ Expression effect is faster than Shiore (one week).

+ Good compatibility with most drugs in general groups.

+ Full effect can be obtained after 4 weeks.

+ Do not affect sexual function.

- Mirasapin, the active substance, is contraindicated in diabetes, arterial hypotension and ascending.

-At the reception, you need to pay attention to driving cars and engage in hazardous work.

-18% of patients had drowsiness, 15% dropped out, and 5% lost weight. Other side effects are allowed at the level of 1-3%.

5. Paroxetine

It belongs to the SIOS group, most often used for severe anxiety, panic, social phobia, nightmares and stress after trauma. Paroxetine can solve the problem of anxiety depression, anxiety and phobia. Take 20 mg once a day.

+ The most powerful stimulant in SIO.

+ Excitement and insomnia will heal quickly.

+ There are several side effects such as vomiting and diarrhea.

+ Suitable for patients with cardiovascular problems.

- Impossible for patients with severe exercise inhibition and mental suppression.

- Pager for pregnant fetus.

6. Fluoxetine

One of the representative antidepressants of the SIOS group. Known as Prozac. Fluoxetine is also known as a stimulant that improves your mood. Patients have feelings of dread, tension, restlessness, and a grim hostility towards others. Depending on adaptation, an average of 20 to 60 mg per day is administered.

+ The impact on the work of the mind is significant.

+ There is no sedative work.

+ A tool that is effective for patients with exercise inhibition and excessive sleepiness during the day.

-On may cause weight loss.

-D diabetes can cause hypoglycemia.

- Not contraindicated if renal function is greatly reduced.

7. Fluvaffosamine

Another SIOS drug. Fullbucamine is similar to fluo-exetin in spills, but has an immediate effect and can be reduced at low cost. The effect is to make the neuron's serotonin reuptake more active. There are various causes of depression and obsessive-compulsive disorder. The average dose per day is 100 mg.

+ Realizes lower prices than conventional projectors.

+ Compared to this, faster operation is possible.

+ Relatively mild side effects (diarrhea, dry mouth, drowsiness).

- Contraindicated in diabetes mellitus.

- Pregnant women - with caution, lactating women - prohibited.

- Nausea in some patients.

8. Thirteen

This is one of the widely used universal drugs of the SIOS group. Treatment of almost all depressions, panic disorders and social phobias. However, in severe clinical cases, teralen may not be effective enough. The usual dose is 50 mg per day.

+ No cardiotoxicity.

+ The psychomotor potential of the patient is not changed.

+ does not add weight.

+ Good compatibility with other antidepressants.

- Sleep disturbances and diarrhea may occur during the first two weeks.

- side effects of a sexual nature

9. Escitalopram

This tool is attributed to Siox. The difference lies in the effect of pressing with involuntary movements (ticking, shaking, biting, tapping). Escitalopram is prescribed to patients with panic, anxiety, phobias, obsessions and behaviors. The daily dose is 20 mg.

+ Effective against life delays.

+ One of the most powerful Saiox.

+ More pronounced thymotropic (improving mood) effect compared to many antidepressants of the same family.

- Some patients experience increased anxiety within 2 weeks of admission.

- May cause gastrointestinal disturbances, insomnia and agitation.

- Used during pregnancy only in extreme cases when breastfeeding is not possible.

10. Venlafaxine

It belongs to the group of schiosins. In addition to inhibiting the reacquisition of serotonin, venlafaxine is also effective against another neurotransmitter, norepinephrine. It is prescribed for various causes of depression, social phobias, anxiety, panic. The usual dose is 150 mg per day.

+ Better tolerated by patients than most tricyclics.

+ More pronounced effect than classic Syoks.

+ Fewer contraindications.

— Common side effects of most antidepressants are nausea, drowsiness, dry mouth, diarrhea, or constipation.

- May increase intraocular pressure.

- Withdrawal syndrome, the most severe of the antidepressants.

This list cannot be used as a recommendation. In any case, before buying, consult your doctor. Stay healthy!

The placebo effect was experienced by most people with high suggestibility. There are many examples of how a simple "vitamin" relieved a headache or how a drop of salt water improved the patient's condition literally before our eyes. Make a reservation. If you do not suspect that you have been given a "dummy", then a "miracle" has happened. It's a "cure" so it should work.

Well, what is a placebo, is it really possible to be cured by the power of thought alone, and what is the mechanism of action of the drug "placebo" on the body - I will tell in the article.

Placebo effect in psychology

Derived from the Latin word "placebo", which translates as "think". A placebo is a substance used as a drug without an apparent therapeutic effect. The therapeutic effect is achieved when the patient believes that "this medicine works." Placebo can be found in the treatment of a number of mental disorders, pain syndromes, asthma, Parkinson's disease, bowel disease, ischemia and hypertension. Placebo is more effective, the higher the degree of obedience of a person.

Here is an example from a long time ago. In the 18th century, TB patients were tested on placebo in a German clinic. At first he was said to be "a new drug to cure disease", brought his own medicine and prescribed the sick. With one month of treatment, 80% of people recovered. As I found out later, this "magic medicine" was normal aspirin, which did not affect the severity of tuberculosis, such as tuberculosis.

Much later, the "ignorance" of the placebo effect was scientifically proven. The scientists found that this was based on unconscious brain function. In other words, the brain determines how a drug affects people before it perceives drug information.

The placebo effect is associated with mental and emotional. A person who wants to be healed believes in the effects of prescribed drugs and thinks that this is the hand of salvation. Currently, vitality is mobilized, the recovery process begins, and the patient's physical and mental state returns to normal.

By the way, the price and appearance of the drug play an important role in the placebo. In other words, the higher the placebo price, the better. Speaking of color, for example, yellow drugs in depression, green medicine relieves anxiety, and white drugs have the effect of "hardening" stomach ulcers.

A disease that can be best treated with a placebo has also been found to be the best treatment. These are the following.

  • Headache … 62%.
  • Depression … 59%.
  • Cold … 45%, 59%.
  • Nausea: 58%.
  • Intestinal disease: 58%.

Placebo - what is it in simple words

The placebo effect was first announced by the American doctor Henry Villa in 1955. He found that taking a placebo (a pill without a drug component) would heal about one-third of the patient. However, the "dummy" has been known for a long time. It was mentioned in the 18th century. At that time, a placebo was called a drug that contains indifferent substances.

Matovay Mudrov, a famous doctor who played an active role at the end of the 18th century to the beginning of the 19th century, used three kinds of powder, plain, gold and silver for treatment. With this remedy, the patient's pain is miraculously relieved. Then, when Moodle died, it turned out that the main ingredient in the "magic" powder was normal crayon.

Another historical example of the Plasbo phenomenon dates back to World War II. During the absence of a cure, he administered physiological saline to shocked soldiers, faking morphine. And the pain has been reduced.

In the late 1970s, scientists proved that Plasbo contributed to the production of endorphins, known as hormones of joy and pleasure, and worked in the same way as drugs. Dr. John Levin Medical Science did an experiment. The patient appears to have improved the physical condition of the patient who gave the pacifier to 40 patients with teeth who were extracting wisdom teeth instead of painkillers. And after the introduction of the antidote morphine, people began to experience pain. Hence, the placebo was found to give a sense of security as well as the patient's head, but the body was also suggested.

Placebo effect in medicine and psychology

Placebos are often used in medicine. It is used to relieve pain in a patient when there are no effective drugs, or to improve the patient's condition when there is doubt about the effectiveness of existing drugs. Also, because of impotence, the doctor may prescribe a "placebo" in the hope that the medicine will work, but in reality it turns out to be a useless substance.

Sometimes a placebo is the only way to avoid conflict between doctors and patients. There are patients who are convinced that they need to take some kind of medication, even if they do not have a medical indication. Therefore, the doctor prescribes a neutral treatment to help the person calm down.

  • Positive (most common). Increases the effectiveness of drugs and treatments.
  • Negative. Neutralize the therapeutic effect of the drug or aggravate the condition.
  • Neutral (very rare). As the name suggests, there is no placebo effect here.
  • Physician approval required. If the patient does not trust the doctor, the placebo effect will work negatively.
  • drug prices. Inexpensive drugs for severe disease also have a negative placebo effect.
  • Availability of medicines The placebo effect increases exponentially if you take medicines delivered from far away.

Placebos are also used in new drug trials. As a rule, the subjects are divided into two groups: one receives the active drug, and the other receives a "double" dummy. The participants in the experiment did not know what was a placebo and what was a real medicine. The researchers then analyze the results and evaluate the effectiveness of the new drug.

In psychology, the placebo effect is the effect that results from contact with our subconscious. As mentioned earlier, the more suggestive it is, the greater its effect.

Placebos give good results in the treatment of psychosomatic disorders. For example, if the patient himself invents a disease, it should be influenced psychologically, and not with the help of drugs. In this case, the task of the specialist is to convince the patient that the prescribed drug is not a dummy, but a miracle cure for a 100% recovery.

The nocebo effect: the other side of the coin

The placebo effect can also work negatively. This is when the patient expects side effects or worsening of well-being from the "placebo". This effect is called nocebo. Negative expectations are one of the main reasons for this phenomenon. After all, thoughts can have a very strong influence on emotions. The brain creates false sensations that are indistinguishable from real sensations. For example, the fear of pain leads to its intensity.

  • prone to anxiety and depression.
  • have a chronic disease;
  • I have a history of treatment failure.

Overview In many cases, the placebo effect speeds up recovery. However, it is less reliable than the effects of real drugs. Placebos provide a subjective improvement in symptoms but rarely cure the disease. In any case, it must be clearly understood that the placebo effect will work only if the person has a firm belief in recovery, a positive attitude and confidence in the success of the treatment.

Can antidepressants be bought without a prescription? What mood-enhancing drugs work best if you need a milder or stronger one, how they affect your body, and whether they can be taken alone. When choosing a drug, it is important not to harm your health.

I'm depressed!

Often heard from a friend or read on a bulletin board. However, those who make such remarks are fundamentally wrong. After all, what does “depression” mean in conversation? It usually refers to deterioration, frustration and fatigue in the short term and due to the consequences of the situation. Sometimes some people call it depression just because "I have something bad" or "I'm sick."

Modern people are always tense. The overflow of work, the intensity of life, the high demands on oneself and the vast information that flows everywhere. Many people cannot cope with many stressors, so it is not surprising that various symptoms will appear.

  • anxiety?
  • get annoyed?
  • Tired?
  • Sleeping disorder
  • Obsession
  • panic disorder

Do not panic if these symptoms naturally disappear within a short period of time. In most cases, only a good rest is useful for their victory. However, sometimes vacation alone is unsatisfactory and requires little help in the body. To do this, it is very important to choose the right tool.

What depression really is

This is accompanied by many additional symptoms, such as prolonged (two weeks or more) mood, reduced activity, decreased mental activity and lack of enjoyment of life. In other words, if you are not touching your usual joys such as hobbies, family and friends, then you need to take this opportunity, observe your condition and ask a doctor to get to you.

If you do not touch your usual joy, this is an opportunity to think, and in some cases you will need to consult.

This depression is often severe and the psychiatrist needs to be forcibly treated with a specific drug.

What medications are used to treat depression?

There is a common name called antidepressant. It should be noted that the adaptation of antidepressants has increased significantly in recent years. There have been a number of studies not only for depression, but also that antidepressants are effective for anxiety, sleep disorders (insomnia), neurosis, and neurophyllic pain. Today, psychiatrists, neurologists, and even therapists widely prescribe antidepressants of various groups.

The most commonly used medicines of the two groups.

Min based antidepressant

These are the oldest drugs that are the most powerful.

    - a drug with a strong sedative effect and a strong antidepressant effect. A large administration is used to treat severe depression, while a small administration is used for mild disability. There are also sleeping pills, relieving anxiety. -Balanced drugs are usually more familiar than amitripine and relieve anxiety. He has excitement and is designated as Trump's card for depression.

Selected serotonin inverse inhibitor (SIOS)

This is a more modern drug group. The advantage is that they are good at resisting, have few or no side effects.

Often assigned by this group.

    -Sodetsya analgesic effect and a good antidepressant. By using it for a long time, broken dreams are normalized.

    - The antidepressant is quite strong during the day. Relieves anxiety and obsession without the need for sleep. - to the degree of awakening and is often prescribed for the treatment of panic disorder.

Most modern antidepressants have few side effects and are well tolerated.

However, strong antidepressants cannot be sold without a prescription. They can only be prescribed by doctors, such as psychiatrists, neurologists, and sometimes therapists.

Why can't I take antidepressants without a prescription?

  • Only a doctor can assess the risk of side effects for a particular patient.
  • Different types of antidepressants have different nuances in their therapeutic effects. If you choose the wrong medicine, at best it will do you no good, and at worst it will harm you.
  • The choice of dosage is made individually. A rapid increase in dosage on your own can have many unpleasant consequences.
  • Also, elimination should be carried out gradually under the guidance of a physician. Otherwise, you risk getting a withdrawal syndrome.

What to do?

Many medicines are sold without a prescription. It does not work for clinical depression, but it helps with stress, short-term sleep disturbances and irritability. With their help, I try to alleviate my state of mind.

    - one of the most popular means. The most popular dish. May be useful for mild sleep disturbances. It has an anti-anxiety effect and eliminates fear, tearfulness and irritability. It is used to treat phytovascular dystonia, and in alcoholics to relieve withdrawal symptoms. You will not become addicted. It should be borne in mind that it is contraindicated in children under 18 years of age. It has a rather strong sedative effect, causes nervousness and irritability. Effective for concentration, memory and reducing fatigue. Helps restore the nervous system during times of stress.
    Better understanding, relieves frustration and anxiety, improves sleep. During treatment, it is not recommended to engage in activities that require concentration, such as driving a car. Contains extracts of valerian, lemon balm and mint. It has a sedative and anti-anxiety effect. It works well for symptoms such as excitability, emotional instability, and tearfulness. It can be used in the complex treatment of mild restless depression, facilitating the withdrawal of potent drugs. • Increases the body's resistance to stress. Lack of magnesium can lead to nervous system imbalance, irritability and sleep disturbances, so Magne B6 can help in these situations too. It has calming, sedative and anti-anxiety properties and helps treat anxiety, mental and emotional stress. Relieves irritation and tension. It can also be used for neurotic symptoms.

When should I see a doctor?

  • If mood deterioration persists for more than 2 weeks and initial therapeutic efforts have failed.
  • If you have lifeless or suicidal thoughts.
  • Depression significantly impairs normal life, such as being unable to work, being unable to communicate well with family members, and being unable to enjoy the things that used to make you happy.

You can consult a psychiatrist in confidence. Information related to the complaint, not to mention diagnosis and treatment, is considered confidential medical information and will not be shared or disclosed in the workplace. It is better to diagnose depression early and start treatment than to bring it to a neglected state.

According to WHO, more than 40% of people on earth suffer from allergies. And this number is increasing every year. Doctors and scientists have never been able to figure out why such diseases occur. Lack of knowledge prevents us from developing a way to permanently get rid of allergies.

However, in connection with the development of science, today many drugs are produced for strong suppression of expression. Allergically proven tablets eliminate most allergic reactions and help to forget about unpleasant symptoms for a long time.

What is this disease

Allergy is a very strange disease. Since it is not caused by microorganisms, it is not contagious. Allergic reactions are “caused” by our own immune system, which reacts very aggressively to completely harmless substances. Main allergens: house dust, animal hair, plant pollen, product ingredients. As a result of pathological changes in the immune system, the body reacts to these substances and begins to produce antibodies that trigger an inflammatory response.

  • sneeze
  • cough
  • shortness of breath
  • Appearance of itching in the nose and discharge
  • Pimples
  • skin rash

A bright type of disease has less pronounced symptoms. However, symptoms can get worse for a variety of reasons.

If you have symptoms of an allergy, you should consult an allergist. Your doctor will order tests that will allow you to "detect" the allergen. By doing so, you can avoid contact and prevent an aggravation. However, complete separation from allergens can not always be avoided. In this case, drug therapy is carried out to eliminate or reduce the severity of the reaction.

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Allergy remedy

These drugs belong to the group of antihistamines. Prevents the production of histamine. This substance normally participates in many physiological processes. However, if the immune system is disrupted, histamine is actively produced as allergens enter the body. When ingested in large quantities, an inflammatory reaction occurs and allergic symptoms appear. There are currently three generations of antihistamines in medicine.

First generation product

Relieve unpleasant symptoms quickly, but don't overdo it. And this long-term use is addictive. There seem to be side effects.

  • drowsiness
  • weakness
  • reaction suppression
  • Headache

But where there are disadvantages, drugs have advantages. These inexpensive drugs are available not only in the form of tablets, but also in the form of solutions, and are also used for emergency care.

The most popular among them. Not all are suitable for children, so be sure to consult a pediatrician before use.

second generation drugs

It is more effective, practically does not cause drowsiness and has fewer side effects. Work up to 8-12 hours. Some of its features can cause heart rhythm disturbances. The most popular antiallergic agent.

third generation drugs

The drug is not yet fully developed officially. However, unofficially, advanced second-generation drugs include drugs of newer generations. They are characterized by high efficiency, instant effect and a small number of side effects. It is non-addictive and can be used for a long time.

One of the most popular allergy sufferers is Elios. Available in the form of tablets and syrup. Other Modern Remedies

Best Allergy Remedy Today

Corticosteroids and histiocytic membrane stabilizers are used in addition to antihistamines for severe allergic symptoms. Food supplements can also be used as an allergy countermeasure. However, its use requires the consent of the doctor.

How to get rid of allergies forever

Antihistamines, even the most modern ones, only relieve the symptoms, they do not cure the disease. Currently, the most reliable way to eliminate allergies is immunotherapy (ASIT), in which substances that cause allergic reactions are introduced. With a gradual increase in dosage, symptoms of intoxication of the body with an allergen are formed.

AIS can significantly reduce allergies, reduce the duration of exacerbations, and often cure the disease. The disadvantage of immunotherapy is its duration (3-5 years).

  • Wash your hair and shower every night before bed to wash pollen from your skin and hair.
  • Rinse your nose daily. Even rinsing with plain water can help soften harmful particles that have settled on the mucous membranes of the respiratory tract.
  • Washing clothes in hot water at 30-40°C does not kill bed bugs, which are among the most common allergens.
  • It is also important to use a vacuum cleaner to remove dust from carpets and upholstered furniture.

Unfortunately, there is no universal approach to allergies. In addition, it often takes a long time to find the right fund. If you have any allergic symptoms, consult your doctor and let him choose a treatment method in accordance with the characteristics of your body.

There are contraindications. Need to see a specialist

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Buying a good blood pressure medicine is not easy. The pharmacist at the pharmacy is rarely helpful and will send you to a doctor immediately. Is it really so difficult to recommend a reliable drug at an affordable price? Try to understand the types of drugs and the principle of administration.

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Hypertension

Most people today have never heard of the term "hypertension". It is not surprising that in today's society, one in three faces this problem and is forced to look for a solution.

Blood pressure 140/90 mmHg Art. defined as hypertension. Art and above, regardless of age. In many cases, increased pressure is an independent disease called hypertension. However, high blood pressure can also be a symptom of other conditions (such as kidney, thyroid, or adrenal problems). In this case, it is necessary not only to reduce the figure, but also to treat the underlying disease.

Symptoms

Symptoms of high blood pressure include:

  • Headache
  • headache, headache, dizziness, dizziness, headache, headache, dizziness
  • Dizziness; pre-fainting state; "warmth" before the eyes.
  • In such cases, it is recommended to check blood pressure. If the threshold is exceeded, care should be taken to reduce it.

Can your blood pressure go up even if you're not worried about anything? Unfortunately, such cases are not rare. That's why it's so important to keep your blood pressure under control, even if it seems normal. It seems that many people misunderstand that if there are no symptoms, then there is no need to lower the barometric pressure. Indeed, why take medication when you are in good physical shape? Unfortunately, the rate of complications of high blood pressure is not determined by whether you feel it or not.

High blood pressure can lead to serious complications.

Terrible complications.

Myocardial infarction?

  • Stroke?
  • renal failure.
  • The higher the pressure, the higher the risk of its development.

Most people with high blood pressure need medication to lower their blood pressure. In the early stages, when blood pressure is slightly elevated, lifestyle changes (diet, weight loss, stress relief, exercise) can bring the values ​​back to normal. However, most patients still require ongoing treatment. If treatment is interrupted, high blood pressure and associated discomfort and risk of complications reappear. During treatment, it is very important to control the level of pressure and keep a diary, recording the patient's performance. This allows you to choose the optimal treatment and accurately evaluate its effectiveness.

Treatment

There are many drugs available today to lower blood pressure. Consider the main groups of these drugs.

ACE inhibitor

This medicine inhibits (blocks) one of the enzymes involved in hypertension and is often used as the first line of treatment for hypertension.

Advantages of this group

Does not affect the heart rate (possible prescription by index).

  • Does not increase cholesterol and blood sugar levels.
  • In diabetes and chronic kidney disease, it can not only lower blood pressure, but also prevent the development of kidney failure.
  • These drugs are also effective in chronic heart failure.
  • But for pregnant (or planning to become pregnant) women, this group is not suitable - it can adversely affect the fetus. Also, taking these medicines can sometimes cause a dry cough. If the patient's anxiety is great, it should be replaced with drugs from other groups.

ACE inhibitors are not suitable for pregnant women as they may harm the fetus.

Angiotensin receptor blockers (ARBs).

The mechanism of action is similar to the previous group of drugs, but blocks the process at a different level. In general, they have properties similar to those of ACE inhibitors. If you develop a dry cough while taking an ACE inhibitor, this group is often prescribed because it does not have these side effects.

beta-blockers

Reduces the pressure that acts on the β-adrenaline receptor in the heart and blood vessels.

These drugs not only lower blood pressure, but also increase the pulse rate. It is preferable when the heartbeat is frequent, but it is better not to take it if the pulse is irregular. When choosing doses and treatments, pulse monitoring is required (preferably 50 or more per minute).

It is also recommended for high blood pressure, coronary artery disease and chronic heart failure. In addition, when used in combination with bronchial asthma or chronic obstructive pulmonary disease (COPD), caution must be taken as convulsive bronchodilation may be exacerbated.

Calcium antagonist

Lowers blood pressure by acting on calcium cells in cells. It can be used along with hypertension such as asthma, COPD, diabetes, and kidney disease.

Dirtiazem, Bella Pamil, Isoptine (extended type) - impulse-lowering effect can be used as a substitute for β-blockers.

It does not create Corda Flex, Normodipine, Lelkame n-pulse and has vasodilatation. In particular, it is effective for increasing the expansion of blood pressure (descending blood pressure).

Diuretics

Indpamid Leviard

    ; ; ;
  • Additional water and sodium are discharged outside the body. In particular, it is associated with people who have signs of edema and heart failure. Although the diuretic effect is not the strongest in the Indian pamid and has few side effects, it has a good blood pressure stabilizing effect.

Diuretics are suitable for people with signs of heart failure.

This group should be used with caution to increase blood sugar and uric acid levels.

Central nervous system

Reduces the pressure that acts on the brain receptor. In principle, if the desired effects cannot be obtained, it is added in combination with other drugs.

Complex instrument

In the treatment of high blood pressure, some combination of active substances is often used. According to studies, the combination is more effective than increasing the number of drugs and has fewer side effects. Many co-administered drugs complement each other's effects and improve each other.

As a result, many agents containing two agents in one tablet, and sometimes three agents at the same time, are produced. The technology is efficient and very convenient.

2. combined use

ACE inhibitor + Diuretic: ANAP N, Codlon, Noryprel.

  • Angiotensin receptor antagonist + diuretics: Rosla Plus, Balsacall N, Ederby KL.
  • Angiotensin receptor antagonist + calcium antagonist: LOL Tenza, Veroset, ex.
  • Beta blocker + calcium antagonist: Concole AM, Logimax.
  • 3 combined use
  • ACE blocker + diuretic + calcium antagonist: KO DARNEF, Trick LAX.

Angiotensin receptor antagonist + diuretics + calcium antagonist: co-vamloset, Coxford.