Is haldol addictive. Haloperidol Efficacy and Safety in Alcohol Addicts: CYP3A4 Activity Correlation Study
How does CYP3A4 enzyme activity impact haloperidol effects in alcohol addicts. What is the correlation between CYP3A4 activity and haloperidol efficacy and safety. How can understanding CYP3A4 activity improve treatment outcomes for alcohol addiction.
Understanding Haloperidol and Its Metabolism in Alcohol Addiction Treatment
Haloperidol is a widely used antipsychotic medication that plays a significant role in treating various psychiatric conditions, including alcohol addiction. As a potent dopamine receptor antagonist, it effectively blocks mesolimbic postsynaptic dopamine receptors, contributing to its antipsychotic properties. However, the use of haloperidol in alcohol abusers is not without challenges.
The metabolism of haloperidol involves several enzymatic processes:
- Cytosolic carbonyl reductase reduces haloperidol to its reduced form, which retains 10-20% of the parent molecule’s activity.
- CYP3A4 further metabolizes the reduced form to a tetrahydropyridine, followed by glucuronidation and sulphation.
- CYP3A4 and CYP2D6 can back-oxidize reduced haloperidol to its original form.
- N-dealkylation of haloperidol by CYP3A4 and CYP2D6 produces 4-chlorophenyl-4-hydroxypiperidine and p-fluorobenzoyl propionic acid.
Understanding these metabolic pathways is crucial for optimizing haloperidol treatment in alcohol addicts, as variations in enzyme activity can significantly impact drug efficacy and safety.
The Role of CYP3A4 in Haloperidol Metabolism and Its Clinical Implications
CYP3A4 is a key enzyme involved in the metabolism of haloperidol. Its activity can vary among individuals, potentially affecting the drug’s effectiveness and side effect profile. Researchers have been investigating the correlation between CYP3A4 activity and haloperidol’s biotransformation rate, with some studies showing a significant relationship while others remain inconclusive.
Why is understanding CYP3A4 activity important in haloperidol treatment for alcohol addicts? The enzyme’s activity can influence:
- The rate at which haloperidol is metabolized
- The concentration of active drug in the body
- The occurrence and severity of side effects
- The overall efficacy of the treatment
By assessing CYP3A4 activity, healthcare providers may be able to personalize haloperidol dosing and improve treatment outcomes for alcohol addicts.
Investigating CYP3A4 Activity and Haloperidol Effects: A Clinical Study
A recent study aimed to explore the correlation between CYP3A4 isoenzyme activity and the efficacy and safety of haloperidol in alcohol abusers during addiction exacerbation. The research involved 15 male patients hospitalized at the Moscow Research and Practical Centre for Narcology.
How was CYP3A4 activity measured in the study? Researchers employed high-performance liquid chromatography with mass spectrometry (HPLC/MS) to determine the ratio of cortisol to 6-beta-hydroxycortisol in urine samples. This ratio serves as an indicator of CYP3A4 activity, as the enzyme is responsible for the conversion of cortisol to its metabolite.
Assessment Tools and Metrics
To evaluate the efficacy and safety of haloperidol treatment, the study utilized several standardized scales:
- The National Research Center on Addictions scale for addiction severity
- Hamilton Anxiety Research Scale (HARS) for anxiety assessment
- UKU Side-Effect Rating Scale for monitoring adverse effects
These tools provided a comprehensive view of the clinical picture, allowing researchers to quantify the impact of haloperidol treatment on addiction symptoms and overall patient well-being.
Challenges in Haloperidol Use for Alcohol Addiction Treatment
While haloperidol can be effective in managing certain symptoms associated with alcohol addiction, its use is not without challenges. Alcohol abusers often have ambiguous or negative attitudes towards haloperidol, which can limit its application in addiction treatment.
What factors contribute to the reluctance in using haloperidol for alcohol addiction? Several issues come into play:
- Potential for unwanted adverse effects
- Misconceptions about antipsychotic medications
- Fear of developing dependence on another substance
- Lack of understanding about the medication’s role in addiction treatment
Addressing these concerns through patient education and careful monitoring can help improve acceptance and adherence to haloperidol treatment in alcohol addicts.
Personalized Medicine: Tailoring Haloperidol Treatment Based on CYP3A4 Activity
The growing field of personalized medicine offers promising applications in addiction treatment, particularly when it comes to medications like haloperidol. By understanding individual variations in CYP3A4 activity, healthcare providers can potentially optimize treatment regimens for better outcomes.
How can CYP3A4 activity information be used to personalize haloperidol treatment?
- Dose adjustment: Patients with higher CYP3A4 activity may require higher doses to achieve therapeutic effects, while those with lower activity might need lower doses to prevent side effects.
- Monitoring frequency: Individuals with extreme CYP3A4 activity levels may benefit from more frequent monitoring of drug levels and side effects.
- Combination therapy: Understanding CYP3A4 activity can help in selecting appropriate adjunct medications that don’t interfere with haloperidol metabolism.
- Predicting treatment response: CYP3A4 activity levels may serve as a biomarker for potential treatment efficacy and side effect risk.
By incorporating CYP3A4 activity assessment into clinical practice, treatment plans can be tailored to individual patient needs, potentially improving both efficacy and safety profiles of haloperidol in alcohol addiction treatment.
Implications for Future Research and Clinical Practice
The study investigating the correlation between CYP3A4 activity and haloperidol effects in alcohol addicts opens up several avenues for future research and clinical applications. As our understanding of the relationship between enzyme activity and drug response grows, we can anticipate advancements in addiction treatment strategies.
What are some potential areas for future investigation?
- Larger-scale studies to confirm and expand upon the current findings
- Development of rapid CYP3A4 activity testing methods for clinical use
- Exploration of other cytochrome P450 enzymes and their impact on addiction medications
- Integration of genetic testing to predict CYP3A4 activity and drug response
- Investigation of potential CYP3A4 modulators to optimize haloperidol treatment
These research directions could lead to more precise and effective treatment protocols for alcohol addiction, potentially improving patient outcomes and reducing the burden of addiction on individuals and society.
Ethical Considerations in Pharmacogenetic Approaches to Addiction Treatment
As we move towards more personalized approaches in addiction treatment, including the use of pharmacogenetic information like CYP3A4 activity, it’s crucial to consider the ethical implications of these advancements. The integration of genetic and enzymatic data into treatment decisions raises important questions about patient privacy, consent, and potential discrimination.
What ethical considerations should be addressed in pharmacogenetic-based addiction treatment?
- Informed consent: Ensuring patients understand the implications of genetic testing and how it may influence their treatment.
- Data privacy: Implementing robust measures to protect sensitive genetic information from unauthorized access or misuse.
- Equitable access: Addressing potential disparities in access to pharmacogenetic testing and personalized treatment options.
- Stigma and discrimination: Safeguarding against the misuse of genetic information that could lead to discrimination in employment, insurance, or other areas.
- Cultural sensitivity: Considering how pharmacogenetic approaches may be perceived and accepted across different cultural backgrounds.
By proactively addressing these ethical concerns, the medical community can ensure that advancements in personalized addiction treatment benefit patients while protecting their rights and dignity.
The Potential Impact of CYP3A4 Research on Addiction Treatment Policies
The growing body of research on CYP3A4 activity and its relationship to haloperidol efficacy in alcohol addiction treatment has the potential to influence healthcare policies and guidelines. As evidence accumulates, policymakers and healthcare organizations may need to reassess current approaches to addiction treatment and medication management.
How might CYP3A4 research impact addiction treatment policies?
- Incorporation of pharmacogenetic testing into standard treatment protocols
- Development of guidelines for personalized dosing based on CYP3A4 activity levels
- Revision of monitoring requirements for patients on haloperidol and similar medications
- Integration of CYP3A4 testing into electronic health records for improved decision support
- Allocation of resources for further research and implementation of personalized medicine approaches in addiction treatment
These policy changes could lead to more effective and safer treatment strategies for alcohol addiction, potentially reducing healthcare costs and improving patient outcomes in the long term.
Challenges in Implementing CYP3A4-Based Treatment Approaches
While the potential benefits of incorporating CYP3A4 activity assessment into alcohol addiction treatment are significant, there are several challenges that need to be addressed for successful implementation:
- Cost considerations: Developing and implementing widespread CYP3A4 testing may require substantial financial investment.
- Training and education: Healthcare providers will need comprehensive training on interpreting and applying CYP3A4 activity data in clinical practice.
- Standardization: Establishing standardized protocols for CYP3A4 testing and result interpretation across different healthcare settings.
- Integration with existing systems: Incorporating CYP3A4 data into current electronic health record systems and clinical decision support tools.
- Patient acceptance: Addressing potential concerns or resistance from patients regarding genetic testing and personalized treatment approaches.
Overcoming these challenges will require collaboration between researchers, healthcare providers, policymakers, and patient advocacy groups to ensure the successful integration of CYP3A4-based approaches into addiction treatment.
The Future of Addiction Treatment: Integrating Pharmacogenetics and Personalized Medicine
As research on CYP3A4 activity and its impact on haloperidol treatment in alcohol addiction continues to evolve, it represents just one aspect of a broader shift towards personalized medicine in addiction treatment. The future of addiction care is likely to involve a more comprehensive approach that considers multiple genetic, environmental, and personal factors to tailor treatment plans.
What elements might be included in future personalized addiction treatment approaches?
- Comprehensive genetic profiling to assess multiple drug-metabolizing enzymes and neurotransmitter systems
- Integration of biomarker data, including CYP3A4 activity, to guide medication selection and dosing
- Use of artificial intelligence and machine learning algorithms to predict treatment outcomes based on individual patient profiles
- Incorporation of wearable technology and digital health tools to monitor patient progress and adjust treatment in real-time
- Development of targeted therapies based on specific genetic and metabolic profiles associated with addiction vulnerability
These advancements have the potential to revolutionize addiction treatment, moving away from one-size-fits-all approaches towards more precise, effective, and patient-centered care strategies.
The Role of Interdisciplinary Collaboration in Advancing Addiction Treatment
To fully realize the potential of personalized medicine in addiction treatment, including the application of CYP3A4 activity assessment, interdisciplinary collaboration will be essential. This collaborative approach brings together experts from various fields to address the complex nature of addiction and its treatment.
Which disciplines should be involved in advancing personalized addiction treatment?
- Pharmacology and pharmacogenetics
- Addiction medicine and psychiatry
- Molecular biology and genetics
- Bioinformatics and data science
- Clinical psychology and behavioral therapy
- Public health and health policy
- Bioethics and law
By fostering collaboration among these diverse fields, we can accelerate the development and implementation of more effective, personalized approaches to addiction treatment, ultimately improving outcomes for individuals struggling with alcohol addiction and other substance use disorders.
CYP3A4 activity and haloperidol effects in alcohol addicts
. 2015;27 Suppl 1:S23-4.
doi: 10.3233/JRS-150676.
M S Zastrozhin
1
2
, V V Smirnov
3
, D A Sychev
1
, L M Savchenko
1
, E A Bryun
2
, O A Matis
2
Affiliations
Affiliations
- 1 Russian Medical Academy of Postgraduate Education, Moscow, Russia.
- 2 Moscow Research and Practical Centre for Narcology of the Departament of Public Health, Moscow, Russia.
- 3 National Research Center – Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, Russia.
PMID:
26639694
DOI:
10.3233/JRS-150676
M S Zastrozhin et al.
Int J Risk Saf Med.
2015.
. 2015;27 Suppl 1:S23-4.
doi: 10.3233/JRS-150676.
Authors
M S Zastrozhin
1
2
, V V Smirnov
3
, D A Sychev
1
, L M Savchenko
1
, E A Bryun
2
, O A Matis
2
Affiliations
- 1 Russian Medical Academy of Postgraduate Education, Moscow, Russia.
- 2 Moscow Research and Practical Centre for Narcology of the Departament of Public Health, Moscow, Russia.
- 3 National Research Center – Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, Russia.
PMID:
26639694
DOI:
10.3233/JRS-150676
Abstract
Background:
Haloperidol is one of the most commonly used typical antipsychotics [2]. It has a powerful antipsychotic activity blocking mesolimbic postsynaptic dopamine receptors. Unwanted adverse effects accompany the use of haloperidol. Therefore alcohol abusers’ attitudes towards haloperidol are ambiguous and often negative, which sometimes limits it’s use in patients with addictive disorders [3]. Cytosolic carbonyl reductase reduces haloperidol to reduced form, which has 10-20% of the activity of the parent molecule. It is further metabolized by CYP3A4 to a tetrahydropyridine and then conjugated by glucuronidation and sulphation. Reduced haloperidol is back-oxidized to haloperidol by CYP3A4 and CYP2D6. Haloperidol is N-dealkylated by CYP3A4 and CYP2D6 to 4-chlorophenyl-4-hydroxypiperidine and p-fluorobenzoyl propionic acid. The correlation between CYP2D6 and CYP3A4 activity and the rate of biotransformation of haloperidol was demonstrated in a number of studies on patients with schizophrenia [1, 2, 5]. At the same time other studies deny or disaffirm this correlation [4].
Objective:
To estimate the correlation between CYP3A4 isoenzyme activity and the efficacy and safety of haloperidol in patients with alcohol abuse during the exacerbation of the addiction.
Methods:
The study involved 15 men, alcohol abusers, in exacerbation of their addiction, who were hospitalized in Moscow Research and Practical Centre for Narcology of the Departament of Public Health. All 15 patients received haloperidol in tablets and injections. Determination of CYP3A4 activity was performed using high performance liquid chromatography with mass spectrometry (HPLC/ MS) by determination of endogenous substrate of this isoenzyme and its metabolite in urine – the ratio: cortisol/6-beta-hydroxycortisol. We used international psychometric scales to assess efficacy of haloperidol (the scale of determining the severity of addiction of The National Research Center on Addictions of the Ministry of Health Of Russia, Hamilton Anxiety Research Scale (HARS)). The safety of haloperidol was estimated by the UKU Side-Effect Rating Scale. Scales express the clinical picture of the abuse. The higher the score, the more pronounced the addiction is. Calculating the differences in scores of the scales allowed for clinical assessment of haloperidol effects. The larger the difference in scores was, the more pronounced were the changes in clinical picture of abuse, and the higher the efficacy of therapy was assumed. Statistical analysis of the results of the study was performed by non-parametric statistics by the program STATISTICA v10.0 («StatSoft Inc.», USA). The normality of sample distribution was estimated by Shapiro-Wilk’s W-test, and the homogeneity of dispersion, that was estimated by Fisher’s T-test (in case of comparison of two samples). The differences were evaluated as significant in case of p < 0,05 (statistic power >80%). To determine the correlation between the quantitative characteristics Spearman rank R coefficient was calculated. The value of correlation coefficient r from 0,3 to 0,7 (p < 0,05) indicated positive moderate, but significant correlation between the characteristics, r>0,7 (p < 0,05) – strong and significant correlation, negative value of r indicated inverse correlation.
Results:
Data analysis demonstrated a correlation between the activity of isoenzyme CYP3A4 and the scores of pathological addiction (r1 = -0,36), HARS (r2 = -0,45), UKU Side-Effect Rating Scale (r3 = -0.15) in the entire group (p < 0.05). In a group of patients, who received the higher doses of haloperidol (more than 7.5 mg per day in tablets or 5 mg per day in injections), the following results were received in the same groups of data: r1 = -0.68, r2 = -0.71, r3 = -0.76 (p < 0.05).
Conclusions:
The results demonstrate the correlation between CYP3A4 activities and the efficacy and safety of haloperidol in alcohol abusers during the exacerbation of the addiction. The inverse correlation indicates that the higher the activity of CYP3A4 is, the lower the efficacy of haloperidol is. Also it can be assumed that the presence of strong correlation between the activity of CYP3A4 and the efficacy of haloperidol in group of patients, who received higher doses of haloperidol, may indicate that CYP3A4 is involved in haloperidol metabolism when it is used at higher doses.
Limitations of the study:
It should be noted that in this research the activity of CYP3A4 was determined using high performance liquid chromatography with mass spectrometry (HPLC/MS) by determination the ratio of cortisol/6-beta-hydroxycortisol for the fist time. To increase the level of our confidence in the results further studies with a larger number of people are necessary.
Keywords:
ABCB1; CYP3A4; Haloperidol; alcohol abuse; biotransformation; side effects.
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Haloperidol: 7 things you should know
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Medically reviewed by Carmen Fookes, BPharm. Last updated on April 6, 2022.
1. How it works
- Haloperidol may be used to treat psychotic thoughts or symptoms. Experts aren’t sure exactly how haloperidol works to reduce psychotic thoughts or symptoms or control tics in Tourette syndrome, but suggest it helps to rebalance neurotransmitters such as dopamine in the brain.
- Haloperidol belongs to the class of medicines known as butyrophenone antipsychotics. It may also be referred to as a typical, conventional, or miscellaneous antipsychotic.
2. Upsides
- May be used in the treatment of schizophrenia.
- May help control tics and vocal utterances of Tourette syndrome. Some studies have reported a 78-91% reduction in tics.
- Available as oral tablets and as an injection. The injection is not approved for intravenous administration.
- Generic haloperidol is available.
3. Downsides
If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:
- Extrapyramidal side effects such as akathisia (a feeling of inner restlessness), Parkinsonism (eg, mask-like face, restlessness, shuffling gait), blurred vision, breast discharge, constipation, dry mouth, dystonia (prolonged abnormal muscle contractions), missed menstrual periods, swallowing difficulties, weakness, and weight gain are some of the more common side effects.
- Haloperidol may cause tardive dyskinesia (potentially irreversible and untreatable, involuntary movements of the tongue, lips, face, trunk, and extremities). The risk is highest among elderly women, and with longer treatment durations or higher dosages. Because of this risk, the smallest effective dose of haloperidol should be used and the need for continued treatment should be reassessed periodically.
- May cause low blood pressure, sleepiness, leukopenia, neutropenia, agranulocytosis, or balance problems, increasing the risk of falls and fall-related injuries.
- May cause ECG changes and heart arrhythmias. The risk is greater with higher dosages and in people with electrolyte imbalances (particularly low potassium or low magnesium levels), concomitant medications known to prolong the QT interval, underlying cardiac abnormalities, hypothyroidism, or familial long QT-syndrome.
- There is considerable individual variation in the amount of haloperidol required for treatment.
- May be associated with a detrimental effect on cognitive function and generally more side effects than other neuroleptics, such as fluphenazine and pimozide, that have also been found to be effective in the treatment of Tourette syndrome.
- Use of antipsychotics in elderly patients with dementia has been associated with an increased risk of death, mostly due to cardiovascular or infectious causes. Haloperidol injection is not FDA-approved for use in elderly patients with dementia.
- Avoid in people with Parkinson’s disease, severe central nervous system depression, comatose states, or with previous hypersensitivity to haloperidol. May not be suitable for some people with certain cardiovascular disorders; receiving anticonvulsant medications or with a history of seizures; mania; or thyrotoxicosis.
- Rarely, may cause Neuroleptic Malignant Syndrome; symptoms include high body temperature, muscle rigidity, and mental disturbances. Discontinue immediately and seek urgent medical advice.
- May interact with several drugs including ketoconazole, paroxetine, those that affect the Q-T interval, or that inhibit or are metabolized by certain hepatic enzymes.
- There are no well-controlled trials on the use of haloperidol in pregnant women. However, cases of limb malformations have been reported following maternal use of haloperidol along with other drugs during the first trimester of pregnancy. Neonates exposed to haloperidol during the third trimester of pregnancy are at risk for extrapyramidal or withdrawal symptoms following delivery. Only use during pregnancy if the benefits outweigh the risks.
Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects
Haloperidol is an antipsychotic medication that may be used in the treatment of schizophrenia and Tourette syndrome. Detrimental effects on cognitive function and movement-related side effects are common.
5. Tips
- Take as directed by your doctor. Haloperidol is usually dosed two to three times daily.
- Avoid alcohol while taking haloperidol as it may contribute to the side effects of haloperidol including low blood pressure.
- Haloperidol may affect your judgment and impair your ability to drive or operate machinery. It may also increase your risk of falls.
- A ‘one-dose fits all’ dosage schedule does not apply to haloperidol. Your doctor may have to adjust your haloperidol frequently on initiation to find the right dose for you.
- Tell your doctor if you experience any unexplained fever, muscle rigidity or unusual muscle movements, agitation, irritability, anxiety, or other uncharacteristic mental disturbances while taking haloperidol.
- Do not take any other medications either on prescription or over-the-counter without talking with a doctor or pharmacist to check that they don’t interact with haloperidol.
- Do not abruptly stop haloperidol. If you need to discontinue haloperidol, your doctor will tell you how to taper it down.
- Ensure you use adequate contraception or are abstaining from sex to avoid pregnancy while taking haloperidol. If you inadvertently become pregnant while taking haloperidol, contact your healthcare provider immediately.
6. Response and effectiveness
Haloperidol is absorbed quickly but it may take a few days to a few weeks for psychotic symptoms or symptoms of Tourette syndrome to abate. The maximum effects are usually seen within four to six weeks.
7. Interactions
Medicines that interact with haloperidol may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with haloperidol. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.
Common medications that may interact with haloperidol include:
- antibiotics, such as erythromycin, isoniazid, quinupristin/dalfopristin, or rifampin
- anticoagulants (blood thinners) such as apixaban, dabigatran, heparin, or warfarin
- anticholinergics, such as scopolamine
- anticonvulsants, such as carbamazepine, phenytoin, or valproic acid
- antihistamines, such as diphenhydramine
- antipsychotics, such as chlorpromazine, fluphenazine, thioridazine, risperidone, or trazodone
- anxiety treatments, such as alprazolam or clonazepam
- appetite suppressants, such as sibutramine
- bipolar disorder medications, such as lithium
- medicines that affect the heart’s rhythm, such as amiodarone, dofetilide, dronedarone, pimozide, quinidine, sotalol, or procainamide.
- muscle relaxants
- pain relievers, such as codeine, hydrocodone, or oxycodone
- Parkinson’s disease treatments, such as carbidopa, levodopa, or selegiline
- sleeping tablets, such as zolpidem
- tricyclic antidepressants, such as amitriptyline, nortriptyline
- Others, such as bupropion, cabergoline, methyldopa, pergolide, sibutramine, theophylline, tramadol.
Avoid drinking alcohol while taking haloperidol.
Note that this list is not all-inclusive and includes only common medications that may interact with haloperidol. You should refer to the prescribing information for haloperidol for a complete list of interactions.
More about haloperidol
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References
- Haloperidol [Package Insert]. Revised 05/2021. Cardinal Health https://www.drugs.com/pro/haloperidol.html
Further information
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Breakdowns in the dopamine system – Maria Paap on vc.ru
Neurotransmitter associated with attention and motor activity
Dopamine is best known as the “hormone of happiness” or neurotransmitter associated with the formation of dependence. However, in addition to these functions, it plays a prominent role in a variety of diseases, including drug addiction, schizophrenia, and Parkinson’s disease.
As researchers have learned more about the biochemistry of the brain and how it works in general, as well as how specific chemicals work, their understanding of this key element has grown by leaps and bounds. As a result, the diagnosis and treatment of dopamine-related diseases are constantly improving.
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What is dopamine?
Chemicals in the brain, such as dopamine, are called neurotransmitters. This word reflects their function – they transmit chemical messages between neurons (brain and nerve cells). Outside the brain, dopamine is a hormone.
Each neurotransmitter performs different functions and affects several areas of the brain. They perform different functions in different areas. For example, in the motor centers of the brain, dopamine is responsible for motor activity. And in the training areas, he works with attention.
To transmit messages through the nervous system, a neurotransmitter “binds” to a receptor specifically designed for it. Just like a key goes into a lock. Dopamine can only interact with neurons that have dopamine receptors.
When the activity of a neurotransmitter is disturbed, this leads to the appearance of symptoms associated with its normal role. This is called neurotransmitter dysregulation .
We hear or read about “low” or “high” levels of dopamine and other neurotransmitters, but in many cases, experts are not sure what exactly causes the symptoms:
- Abnormal levels, as if the brain is producing too much [ 1 ] or too little. [ 2 ]
- Abnormal receptor sensitivity, i.e. “locks” on neurons do not respond properly to dopamine as a “key”.
- Too few receptors, meaning dopamine can interact with fewer neurons.[ 3 ]
- Too many receptors, meaning dopamine can interact with more neurons.[ 4 ]
According to a study published in 2020, the areas of the brain most affected by dopamine are the motor cortex and the insular cortex (lobus insularis), but its influence extends far beyond.[5]
The motor cortex is responsible for the planning, control and execution of voluntary movements. The insular cortex plays a role in maintaining homeostasis, which maintains the body at the right temperature, signals that you are hungry, regulates the heartbeat and breathing, and in general, everything works according to the set parameters.
Relationship with norepinephrine
The body produces norepinephrine from dopamine, they bind to the same receptors and work together to perform many functions. Research suggests they may even be produced and released from the same cells.
How dopamine works
Dopamine is believed to play a role in many important bodily functions, mainly those related to mental performance, emotional response and physical responses.
These include: [ 6 ]
- Behavior involving motivation, punishment and reward
- Cognitive functions including attention, learning and working (short-term) memory
- Free movements
- Pain perception
- Sleep and dreams
- Mood regulation
Although commonly referred to as the happiness hormone, it actually makes you happy only when it comes to rewards and motivation.
For example, when you taste your favorite ice cream, you get a dopamine boost that makes you happier and therefore more motivated to try it again. Even the anticipation of a reward can increase the amount of dopamine in the brain.[ 7 ]
Low dopamine
Symptoms of low dopamine activity can affect many areas of health and life. They vary depending on the area of the brain where dopamine or dopamine activity is lacking.
Symptoms of insufficient dopamine activity include:
- Muscle stiffness, sensation of stiffness and pain.
- Tremor.[ 8 ]
- Muscle cramps or spasms.
- Decreased balance and coordination. [ 9 ]
- Characteristic gait (way of walking), often including small, shuffling steps.
- Impaired fine motor skills (for example, the ability to hold a pencil or thread a needle).
- Constipation.
- Eating and swallowing problems.
- Cognitive impairment (“fog in the head”).
- Difficulties in focusing attention. [ 10 ]
- Fatigue.
- Lack of energy.
- Slow movements or speech.
- Mood swings.
- Low sex drive.
If you have experienced some of these symptoms together, you may not even have known that they might be related. Be sure to tell your doctor about all the symptoms so that you can be properly diagnosed and treated.
High dopamine
High dopamine levels and excessive dopamine activity in the brain can be debilitating, but some symptoms can be seen as an advantage, especially when it comes to learning.
High dopamine activity is associated with:
- Anxiety.
- Excessive energy or manic states.
- Increased feeling of stress.
- Improved concentration and learning ability.
- High sex drive.
- Insomnia.
- Aggression.
- Hallucinations.
Be sure to talk to your healthcare provider if you experience any of these symptoms, especially if you have some of the more severe symptoms such as hallucinations and aggression.
Study doping
The effects of dopamine on learning have led some high school and college students to take dopamine-boosting drugs in the hope of doing better on tests. This practice is not recommended by medical professionals due to the many potentially dangerous side effects.
Concomitant diseases
A wide range of medical conditions are due to dopamine problems. Some of these are considered psychological, others are classified as physiological, and still others may be a mixture of the two. Regardless of how the disease is classified, it is associated with very real disorders in the brain.
Mental illnesses associated with dopamine include:
- Addiction.
- Schizophrenia.
- Depression.
- Bipolar disorder.
- Attention deficit/hyperactivity disorder.
- Obsessive-compulsive disorder.
- Compulsive overeating.
Movement disorders involving dopamine include:
- Parkinson’s disease.
- Huntington’s disease.
- Restless legs syndrome.
Some conditions classified as central sensitization syndromes involve dopamine dysregulation, including:
- Fibromyalgia
- Chronic fatigue syndrome
Dependency
The role of dopamine in reward and motivation is a key aspect of addiction. Whether it’s drugs, food, gambling, shopping, or sex, having “pleasure” gives the brain the pleasurable sensations that dopamine creates. The brain can crave these sensations to an unhealthy degree, and prompts you to repeat the behavior that results in the release of dopamine.
Technology and social media addiction
There is a lot of media coverage of the idea that technology – especially smartphones and social media – is turning many people into drug addicts. It’s a controversial topic, but some experts say it’s a real threat.
Perhaps the constant social media rewards (like getting “likes” and “shares”) set up the same cycle of dopamine release and motivation to repeat the behavior that leads to addiction.
In 2019, the Journal of Behavioral Addictions published a study that showed parallels between people with excessive use of social media and those who abuse psychoactive substances and suffer from behavioral addictions.[ 11 ]
Other mental/behavioral disorders
Some mental and behavioral disorders are associated with dopamine dysregulation.
Schizophrenia
Dopamine plays a role in the mental disorder schizophrenia. Other neurotransmitters, including GABA and glutamate, may also be important. [ 12 ]
Past generation antipsychotics block the action of dopamine in the brain, and the fact that they often relieve symptoms of schizophrenia is strong evidence that dopamine is the culprit. However, some newer antipsychotics also relieve symptoms of schizophrenia without affecting dopamine.
The main symptoms of schizophrenia include:
- Psychosis (altered perception of reality)
- Delusions
- Hallucinations
- Disorganized speech and behavior
Major depressive disorder (clinical depression)
Low dopamine activity is associated with some symptoms of major depression, including lack of interest and motivation.[ 13] The neurotransmitters serotonin and norepinephrine are also believed to be involved in clinical depression, and antidepressants generally target these two neurotransmitters rather than dopamine.
Bipolar disorder
Both high and low dopamine activity have been suggested to be involved in bipolar disorder, providing a possible explanation for the two phases of the disease: manic (extreme highs) and depressive (extreme lows).[ 4]
An excess of dopamine receptors and an overactive reward network may underlie the manic phase of the disease. Meanwhile, decreased levels of a substance called the dopamine transporter may contribute to decreased dopamine function and depression. A common problem may be dopamine regulation, not just highs and lows.[ 4]
Sometimes some symptoms of bipolar disorder are treated with antipsychotics, which reduce dopamine activity.
Attention deficit hyperactivity disorder (ADHD)
ADHD includes difficulties with attention, working memory, impulsivity and hyperactive behavior. This is thought to be due to low dopamine activity, possibly due to certain genetic mutations that affect dopamine. or make dopamine more available to neurons, slowing down certain processes.[ 15 ]
Obsessive Compulsive Disorder (OCD)
Dopamine, along with serotonin and glutamate, is thought to be dysregulated in OCD, an anxiety disorder. With OCD, people have obsessions (intrusive thoughts or images that cause significant emotional distress) and compulsions (behaviors that a person does to reduce upsetting obsessions).
In OCD, there may be a decrease in dopamine receptor activity, as well as increased dopamine activity in some areas of the brain.[ 16] Most OCD medications include antidepressants, which alter the function of serotonin but not dopamine.
Binge eating disorder (BED)
BED involves repetitive, rapid eating of large amounts of food accompanied by feelings of loss of control and feelings of shame, distress, or guilt. Dopamine dysregulation has been proposed as one of the possible biological explanations for this condition, as it is associated with impulse control and reward centers in the brain. [9]0030 17]
BED is sometimes treated with certain medications that can interfere with dopamine.
Movement disorders
The role of dopamine in the motor cortex is very important for the muscles to make smooth, controlled movements. Insufficient dopamine activity in this area is associated with several diseases.
Parkinson’s disease
In Parkinson’s disease, dopamine-producing neurons are destroyed, resulting in a chronic lack of dopamine.
Symptoms occurring include: [ 8 ]
- Tremor
- Stiffness
- Trouble walking
- Balance problems
- Speech and swallowing problems
- Reduced facial expressions
Parkinson’s disease is a progressive disease that gets worse over time. It is treated primarily with drugs that convert to dopamine in the body, increase dopamine levels, or mimic the effects of dopamine.
Huntington’s disease
Huntington’s disease is a progressive genetic disorder with both motor and non-motor symptoms. It is caused by destruction of a part of the brain called the striatum, which is an important part of the motor and reward system.[ 18]
Symptoms of Huntington’s disease include:
In the advanced stages of the disease, people may completely lose the ability to walk and talk. Huntington’s disease may be accompanied by symptoms seen in psychiatric disorders associated with excessive dopamine activity, including psychosis, aggression, and impulsivity. These symptoms are sometimes treated with atypical antipsychotics.
Restless legs syndrome (RLS)
RLS is a movement disorder that is accompanied by strange sensations and involuntary twitching of the legs during sleep or when you are relaxed. These movements can prevent you from getting a deep enough sleep and cause sleep deprivation even after you normally spend enough time in bed.
Some areas of the brain are deficient in iron in people with RLS. In addition, there are abnormal levels of dopamine in the brain. The relationship between low iron levels and high dopamine levels is not yet understood, nor is it clear why these factors cause RLS symptoms.
However, some research suggests that genetics and hormonal abnormalities may also play a role.[ 20] Many of the drugs used to treat RLS are also used to treat Parkinson’s disease.
Syndromes of central sensitization
Central sensitization syndrome is a generic term for a related group of conditions associated with hypersensitivity of the central nervous system, which may include dysregulation of dopamine and other neurotransmitters. This causes abnormal responses to stimuli.
Fibromyalgia
Fibromyalgia may be accompanied by hypersensitivity to pain signals, light, noise, aromas, temperature, and sometimes certain foods. Research indicates an association with low dopamine activity.[ 21]
Symptoms of fibromyalgia that may be associated with dopamine deficiency include:
- Muscle spasms
- Cognitive dysfunction
- Restless legs syndrome
- Sleep problems
- Anxiety
- Depression
- Mood swings
- Difficulty swallowing
Fibromyalgia is not usually treated with drugs that act directly on dopamine, as treatment focuses more on serotonin and norepinephrine.
Myalgic encephalomyelitis (ME/CFS)
ME was formerly referred to as Chronic Fatigue Syndrome (CFS), and these abbreviations are often combined as ME/CFS or CFS/ME.
This is a neuroinflammatory disease associated with low activity of dopamine, serotonin and norepinephrine. It is characterized by extreme fatigue as well as extreme sensitivity to stress and environmental factors (eg noise, heat, chemicals).
Symptoms of ME/CFS that may be associated with low dopamine activity include:
- Cognitive impairment
- Sleep problems
- Anxiety
- Depression
- Mood swings
As with fibromyalgia, ME/CFS treatments often target neurotransmitters other than dopamine. However, the ADHD drug methylphenidate is sometimes prescribed off-label for ADHD,[ 22] and it does increase dopamine levels.[ 23]
Drugs affecting dopamine
Several drug classes are used to treat conditions associated with dopamine dysregulation.
Dopamine agonists
Dopamine agonists increase dopamine levels or function and are used to treat Parkinson’s disease and RLS.
Examples:
- Mirapex (pramipexole)
- Requip (ropinirole)
- Neupro (rotigotine patch)
Typical antipsychotics
Typical antipsychotics reduce dopamine activity in the brain by blocking a key dopamine receptor. They are used to treat schizophrenia and bipolar disorder.
Examples:
- Thorazine (chlorpromazine)
- Navane (thiothixene)
- Haldol (haloperidol)
Atypical antipsychotics
Atypical antipsychotics are newer drugs that reduce dopamine activity in the same way as typical antipsychotics and also affect serotonin. They treat the same conditions as the older generic drugs, but with fewer side effects.
Examples:
- Abilify (aripiprazole)
- Seroquel (quetiapine)
- Clozaril (clozapine)
Notes
1. Brisch R, Saniotis A, Wolf R, et al. (The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue). Front Psychiatry. 2014;5:47. doi:10.3389/fpsyt.2014.00047
2. Masato A, Plotegher N, Boassa D, Bubacco L. (Impaired dopamine metabolism in Parkinson’s disease pathogenesis). Mol Neurodegener. 2019;14(1):35. doi:10.1186/s13024-019-0332-6
3. Gurevich EV, Gainetdinov RR, Gurevich VV. (G protein-coupled receptor kinases as regulators of dopamine receptor functions). Pharmacol Res. 2016;111:1-16. doi:10.1016/j.phrs.2016.05.010
4. Ashok AH, Marques TR, Jauhar S, et al. (The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment). Mol Psychiatry. 2017;22(5):666-679. doi:10.1038/mp.2017.16
5. Li N, Jasanoff A. (Local and global consequences of reward-evoked striatal dopamine release). Nature. 2020;580(7802):239-244. doi:10.1038/s41586-020-2158-3
6. Juárez Olguín H, Calderón Guzmán D, Hernández García E, Barragán Mejía G. (The role of dopamine and its dysfunction as a consequence of oxidative stress). Oxid Med Cell Longev. 2016;2016:9730467. doi:10.1155/2016/9730467
7. Dubol M, Trichard C, Leroy C, et al. (Dopamine transporter and reward anticipation in a dimensional perspective: a multimodal brain imaging study.) Neuropsychopharmacology. 2018;43(4):820-827. doi:10.1038/npp.2017.183
8. National Institutes of Health, National Institute on Aging. (Parkinson’s disease). Updated May 16, 2017.
9. Dan X, Liu J, Doyon J, Zhou Y, Ma J, Chan P. (Impaired fine motor function of the asymptomatic hand in unilateral Parkinson’s disease). front. Aging Neurosci. 2019;11. doi:10.3389/fnagi.2019.00266
10. Kravitz HM, Katz RS. (Fibrofog and fibromyalgia: a narrative review and implications for clinical practice). Rheumatol Int. 2015;35(7):1115-1125. doi:10.1007/s00296-014-3208-7
11. Meshi D, Elizarova A, Bender A, Verdejo-Garcia A. (Excessive social media users demonstrate impaired decision making in the Iowa Gambling Task). J Behav Addict. 2019;8(1):169-173. doi:10.1556/2006.7.2018.138
12. Chen T, Wang Y, Zhang J, et al. (Abnormal concentration of GABA and glutamate in the prefrontal cortex in schizophrenia.-An in vivo 1h-mrs study). Shanghai Arch Psychiatry. 2017;29(5):277-286. doi:10.11919/j.issn.1002-0829.217004
13. Grace AA. (Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression). Nat Rev Neurosci. 2016;17(8):524-532. doi:10.1038/nrn.2016.57
14. Barkley RA, Smith KM, Fischer M. (ADHD risk genes involved in dopamine signaling and metabolism are associated with reduced estimated life expectancy at young adult follow-up in hyperactive and control children). Am J Med Genet B Neuropsychiatr Genet. 2019;180(3):175-185. doi:10.1002/ajmg.b.32711
15. Golmirzaei J, Mahboobi H, Yazdanparast M, Mushtaq G, Kamal MA, Hamzei E. (Psychopharmacology of attention-deficit hyperactivity disorder: effects and side effects). Curr Pharm Des. 2016;22(5):590-594. DOI: 10.2174/13816128282666666615124235816
16. AKOUCHEKIAN S, OMRANIFARD V, MOSHFEGH P, MARACY MR, Almasi A. (The Effect of Atorvastatin On Obssesive-Comp Ulsive Symptoms of Refraactory Obsessive-Compulsive Disorder (Add-on Therapy)). Adv Biomed Res. 2018;7:90. Published 2018 May 29. doi:10.4103/abr.abr_114_16
17. Appolinario JC, Nardi AE, McElroy SL. (Investigational drugs for the treatment of binge eating disorder (BED): an update). Expert Opin Investig Drugs. 2019;28(12):1081-1094. doi:10.1080/13543784.2019.1692813
18. Koch ET, Raymond LA. (Dysfunctional striatal dopamine signaling in Huntington’s disease). J Neurosci Res. 2019;97(12):1636-1654. doi:10.1002/jnr.24495
19. Huntington’s Disease Society of America. (Huntington’s disease stages).
20. Khan FH, Ahlberg CD, Chow CA, Shah DR, Koo BB. (Iron, dopamine, genetics, and hormones in the pathophysiology of restless legs syndrome). J Neurol. 2017;264(8):1634-1641. doi:10.1007/s00415-017-8431-1
21. Albrecht DS, MacKie PJ, Kareken DA, et al. (Differential dopamine function in fibromyalgia). Brain Imaging and Behavior. 2015;10(3):829-839. doi:10.1007/s11682-015-9459-4
22. Blockmans D, Persoons P. (Long-term methylphenidate intake in chronic fatigue syndrome). Acta Clean Belg. 2016;71(6):407-414. doi:10.1080/17843286.2016.1200816
23. Birn RM, Converse AK, Rajala AZ, et al. (Changes in endogenous dopamine induced by methylphenidate predict functional connectivity in nonhuman primates). J Neurosci. 2019;39(8):1436-1444. doi:10.1523/JNEUROSCI.2513-18.2018
Drug therapy for addictions | #08/03
Increasing the effectiveness of the treatment of drug addiction and substance abuse is one of the main problems of narcology. It is not surprising that a significant number of domestic and foreign studies are devoted to the treatment of these conditions (A. G. Gofman et al., 1979; E. A. Babayan, M. A. Gonopolsky, 1987; K. E. Voronin, 1993; T. B. Dmitrieva et al., 1997; A. G. Gofman, A. P. Muzychenko et al., 1999; N. N. Ivanets, M. A. Vinnikova, 2000; Yu. L. Sivolap, V. A. Savchenko, 2000; M. L. Rokhlina, A. A. Kozlov, 2001; P. G. O’Connor et al., 1997; 2001 and more. etc.).
The drug addiction clinic is represented by three main syndromes: mental dependence, physical dependence and tolerance.
Psychological dependence is a painful desire to continuously or periodically take a narcotic or other intoxicating drug in order to experience certain desired sensations or relieve mental discomfort. The most pronounced manifestation of mental dependence is a pathological desire to change one’s state through anesthesia.
Physical dependence is a state of restructuring of the entire functional activity of the body in response to the chronic use of narcotic or other intoxicants. It is manifested by severe physical and mental disorders when the drug is stopped or its effect is neutralized by specific antagonists. These disorders are referred to as abstinence syndrome.
Altered tolerance refers to a state of adaptation (adaptation) to narcotic or other intoxicating substances, characterized by a reduced response to the introduction of the same amount of drug. To achieve the same effect, a higher dose of the drug is required. At the same time, the body of a drug addict can tolerate doses of the drug that are significantly higher than therapeutic and, in some cases, fatal for a healthy person. At a certain stage, tolerance reaches its maximum and remains constant for a long period of time. A further increase in doses no longer causes euphoria (stupefaction), but can lead to overdoses. And finally, in patients with a long duration of the disease, there comes a period when they cannot tolerate the previous high doses of the drug and are forced to reduce the dose.
The task of therapy is to correct the main manifestations of the disease. First of all, this concerns the relief of an acute withdrawal syndrome, which is extremely painful for patients, and the suppression of a pathological craving for a drug – a cardinal addiction syndrome.
It should be noted that in the domestic narcology treatment provides for the complete and immediate deprivation of drugs. The exception is the abuse of sedatives and hypnotics or the combination of other drugs with high doses of these drugs. Treatment with drugs that have a weaker, but narcotic effect, i.e., substitution therapy, is prohibited in Russia.
Treatment of drug addiction and substance abuse is carried out in stages.
The initial stage includes detoxification and relief of acute withdrawal symptoms. It has been proven that chronic intoxication with narcotic drugs causes an imbalance in certain systems of neurotransmission (IP Anokhina, 1982). Therapy aimed at restoring this imbalance contributes to the relief of the main clinical syndromes of drug addiction. Therefore, when choosing therapeutic measures, it is advisable to practice the use of therapeutic agents, the choice of which is pathogenetically justified, in combination with traditional methods of detoxification, as well as psychotropic drugs to eliminate mental disorders observed at this stage. Doses of drugs are selected individually, depending on the severity of a particular symptom. Therapy of the withdrawal syndrome should, if possible, be differentiated and depend on the duration of the disease, the dosages of the drugs used, the psychopathological picture of the disease, and so on.
Among the pathogenetic agents for the relief of acute opium withdrawal syndrome, the following are very effective: clonidine (clophelin) – an agonist of α-2-adrenergic receptors of the central nervous system; tiapridal, an atypical neuroleptic from the group of substituted amines, selectively blocking dopamine D-2 receptors; and tramal (tramadol hydrochloride), a centrally acting analgesic that acts on specific opioid receptors in the central nervous system. The complex use of these drugs allows you to optimally stop the main manifestations of opium withdrawal syndrome.
Clonidine most quickly stops somato-vegetative disorders, but to a much lesser extent affects the psychopathological and algic symptoms and does not suppress the pathological craving for the drug. Tiapridal is highly effective against algic syndrome and partially psychopathological disorders. Tramal has an analgesic effect.
Clonidine is prescribed for the first five to seven days in doses of 0.6-0.9 mg per day. With a drop in blood pressure, the doses of the drug are reduced or it is canceled and cardiotonic drugs are prescribed.
Tiapridal for the first two to three days is prescribed 200 mg three to four times a day intramuscularly, then the same dose orally. After one to two days, the dose is reduced to 100 mg three times a day for another one to two days. The duration of therapy with tiapridal is six to eight days. The effect occurs 10-15 minutes after the injection and lasts about 4 hours. Reduction of pain symptoms is observed already in the first days of treatment. In addition, due to the anti-anxiety and sedative action, tiapridal reduces the severity of the pathological craving for the drug, helps to reduce irritability, irascibility, anxiety, improves sleep and mood. In some cases, tiapridal causes an unexpressed neuroleptic syndrome, which is eliminated either by reducing the dose of tiapridal, or by adding correctors to the therapeutic regimen.
Doses of tramal depend on the dose of the drug used and the patient’s condition: on average, the first two to three days, 2-4 ml (100-200 mg) intramuscularly, then 50-100 mg three to four times a day for another three to four days, gradually reducing the dose. Given that tramal has a partial agonistic effect on opioid receptors, it is very important not to overdose, give it for a short time and stop it in time so as not to cause dependence.
As painkillers, it has recently been proposed to use non-steroidal anti-inflammatory drugs instead of tramal, such as ketorol, xefocam, diclofenac and a number of other similar drugs (N. N. Ivanets, M. A. Vinnikova, 2000; T. N. Dudko et al. , 2001). Ketorol is recommended to be administered in doses of 30 mg (1 ml) intramuscularly or (for mild or moderate pain) one to two tablets per day orally (in one tablet 10 mg). Ksefokam is prescribed for the first four to five days intramuscularly, 2 ml two to three times a day (in one ampoule 2 ml or 8 mg). In the future, while maintaining pain symptoms, they switch to oral administration, one tablet twice a day (in one tablet 4 or 8 mg) until the pain is completely relieved. The duration of treatment with xefocam is five to seven days. (N. N. Ivanets, M. A. Vinnikova, 2000).
There are a number of methods for stopping acute withdrawal symptoms.
Reduce the severity of withdrawal symptoms neuropeptides that normalize the imbalance of catecholamine neurotransmission.
As a means of stopping the opium withdrawal syndrome, a scheme has been developed for the combined use of opiate antagonists (naloxone hydrochloride) with clonidine. In the first days of therapy, maximum doses of clonidine (0.9-1.2 mg) and minimum doses of naloxone (0.2 mg) are prescribed. Then the doses of the first are gradually reduced and the doses of naloxone are increased (up to 1. 8 mg per day). By the end of therapy, the patient receives only naloxone.
In recent years, rapid or ultra-rapid opium detoxification (UROD) has been used, which is carried out under general anesthesia in an intensive care unit. Against the background of anesthesia with the use of muscle relaxants, the patient is intravenously injected with naloxone every half an hour at a dose of 0.8 mg, up to a total of 6 mg of naloxone. Simultaneously, symptomatic therapy is carried out. After the end of UROD, patients are transferred to an anti-relapse naltrexone program.
For the relief of acute opium withdrawal syndrome, a method has been developed for using high doses of atropine. It is described in detail in the guidelines compiled by A. G. Hoffman et al. (1973, 1979). After the development of atropine delirium in patients, withdrawal disorders, primarily autonomic disorders, quickly reverse development, and sleep sets in. The next day, patients complain mainly of general physical weakness and some loss of appetite.
In drug addiction caused by the use of psychostimulants, a combination of drugs that affect dopaminergic mechanisms (bromocriptine), which primarily relieves asthenic disorders and partly neurological disorders, and drugs that affect serotonergic systems that affect the affective symptoms that are so characteristic are used to stop the withdrawal syndrome. for withdrawal symptoms in the abuse of psychostimulants.
Bromocriptine is prescribed in the first days of the withdrawal syndrome in a daily dose of up to 2.5 mg. To stop affective disorders, antidepressants with a predominantly serotonergic component of action are used – fluoxetine, fluvoxamine (floxifral), zoloft (sertraline), paxil (paroxetine), cipramil (citalopram).
With the development of an abstinence syndrome in patients who abuse sedative-hypnotic drugs, it is necessary to reduce drug dosages gradually in order to avoid convulsive seizures and psychoses that can develop in the structure of the abstinence syndrome in this group of patients. Or replacement therapy is prescribed: phenobarbital, pogluferal No. 1, 2, carbamazepine for seven to ten days (depending on the dose of the drug used).
In parallel with pathogenetic therapy, symptomatic treatment is carried out for all forms of drug addiction. Psychotropic drugs (neuroleptics and antidepressants) are used to stop psychopathological disorders, suppress cravings for drugs. Their choice and doses depend on the patient’s condition and the severity of a particular syndrome.
Sleep disturbances are a major problem. To stop insomnia disorders, anxiolytics of the benzodiazepine series (phenazepam, radedorm, rohypnol, reladorm), as well as antipsychotics with a sedative effect (leponex – 12.5-25 mg, chlorprothixene – 50 mg, haloperidol 0.5% – 1.0 ml together with tizercin 2.5% – 1.0 ml intramuscularly).
In addition to medicines, extracorporeal detoxification methods are used to alleviate acute withdrawal symptoms, in particular plasmapheresis (N. N. Ivanets, I. P. Anokhina, N. V. Sagittarius, 1997, G. M. Mitrofanova, 1995).
It is very important to carry out psychotherapy from the very beginning of treatment. The first examination and the first conversation with the patient should already be used as a session of psychotherapeutic influence. Subsequent psychotherapeutic conversations should be aimed at achieving positive attitudes, providing for complete abstinence from drug use, as well as the systematic passage of patient courses of maintenance anti-relapse treatment in out-of-hospital conditions.
After stopping the acute withdrawal syndrome, the so-called post-withdrawal state, or the state of “unstable balance” (IN Pyatnitskaya, 1994), is observed. Psychopathological symptoms, primarily affective and behavioral disorders, come to the fore. Mental disorders often camouflage the exacerbation of a pathological craving for drugs, although patients may not be aware of this. They believe that they have already recovered, they demand to be discharged, not realizing that they are driven by an attraction to change their condition. During this period, the correct choice and use of antidepressants and antipsychotics, corresponding to the clinical manifestations of the patients’ condition, are of particular importance.
Given the characteristics of affective disorders, a significant proportion of dysphoria, agitation, and lack of lethargy in their structure, when choosing antidepressants, preference should be given to drugs with a sedative or balanced effect.
The following antidepressants are recommended: tricyclic – amitriptyline (saroten) – 75-100 mg per day, saroten retard – 50 mg (one capsule per day), anafranil (clomipramine) – 75 mg per day; tetracyclic – maprotiline (ludiomil) – 75-100 mg, lerivon (mianserin) – 60-90 mg, pyrazidol (pirlindol) – 150-200 mg; tricyclic antidepressant of complex chemical structure tianeptine (coaxil) – 37.5 mg; complex bicyclic antidepressant trazodone (trittiko) – 300-400 mg; serotonergic antidepressants – fluvoxamine (floxifral) – 150-200 mg, paroxetine (paxil) – 20-30 mg, zoloft (sertraline) – 50 mg per day, cipramil (citalopram) – 20-40 mg per day.
In severe depression, antidepressants, in particular amitriptyline, can first be administered intramuscularly, then switched to oral administration.
In some cases, drip administration of antidepressants (melipramine, amitriptyline, lyudiomil) is indicated.
It is advisable to combine antidepressants with mild antipsychotics.
Depending on the severity of dysphoria, anxiety, agitation, behavioral disorders, hypochondriacal disorders in patients, eglonil, haloperidol, neuleptil, sonapaks are used. Daily doses of eglonil – 400-600 mg, haloperidol – 4.5-6.0 mg orally or 1-2-3 ml of a 0.5% solution intramuscularly, neuleptil – 20-30 mg, sonapax – 75-100 mg. In the drug addiction clinic, sonapax is most often used to relieve dysphoric disorders and correct the behavior of patients.
With a pronounced asthenic symptom complex, in addition to other therapeutic agents, mild stimulants and nootropic drugs can be prescribed. In some cases, the use of nootropil leads to an exacerbation of the pathological craving for drugs, so it is preferable to prescribe phenibut 0. 5 (two tablets) two to three times a day, aminalon 0.5 (two tablets) three times a day, picamilon 0.02-0 .15 g / day, cerebrolysin.
To correct affective lability, dysphoric disorders, it is recommended to use lithium salts (0.6–0.9per day), carbamazepine (tegretol, finlepsin) – 400-600 mg per day, eglonil (sulpiride) – 400-600 mg per day.
Long-acting and short-acting antipsychotics are used to suppress pathological craving for drugs, relieve dysphoric disorders, and correct behavior.
Among the long-acting drugs, the most effective are piportyl L-4 (pipothiazine palmitate) – 25-50 mg once every two to three weeks intramuscularly; haloperidol-decanoate (haldol-decanoate) – 25-50 mg intramuscularly once every three to four weeks; moditen-depot (fluphenazine-decanoate) – 25 mg once every three to four weeks; fluanxol-depot (flupentixol-decanoate) – 20-100 mg intramuscularly once every two to three weeks; clopixol-depot (zuclopenthixol-decanoate) – 200-500 mg intramuscularly once every two to four weeks.
Among the short-acting antipsychotics – haloperidol – 4.5-6.0 mg per os or 1-2 ml of a 0.5% solution two to three times a day; aminazine (chlorpromazine) – 75 mg per day per os or 1-4 ml of a 2.5% solution intramuscularly; tizercin (levomepromazine) – 50-75 mg per day; stelazin (trifluoperazine) – 15-20 mg per day; etaperazine (perphenazine) – 12-30 mg per day; rispolept (risperidone) – 4-6 mg per day; topral (sultopride) – 400-800 mg per day per os or intramuscularly; fluanxol (flupentixol) – from 3 to 80 mg per day; clopixol (zuclopenixol) – 200-400 mg per day.
Neuleptil (periciazine) is also recommended for correcting the behavior of patients, stopping irritability – 30-40 mg per day; sonapax (thioridazine) – 100-125 mg, clopixol (zuclopenthixol) – 200-400 mg per day; chlorpromazine – 50-75 mg per day, eglonil (sulpiride) – up to 600 mg per day.
Often, in patients with heroin addiction in the post-abstinence period, psychopathic-like behavior is observed, accompanied by severe anxiety, depressed mood, and dysphoria. The occurrence of such conditions usually indicates an exacerbation of craving for drugs. They can be stopped by prescribing, in addition to the other agents mentioned above, a combination of haloperidol with amitriptyline intramuscularly, 2.0 mg of each drug two to three times a day.
As a result of long-term drug use, a psychoorganic syndrome develops in some patients. Moreover, cognitive disorders are transient in nature, after the cessation of drug use, their severity decreases, but a complete recovery is not observed. In addition, at different stages of the disease, patients have apathetic-abulic and peculiar asthenic conditions. In this regard, it can be recommended to include the peptidergic nootropic drug cerebrolysin into the therapeutic program (M. L. Rokhlina, A. A. Kozlov, 2001, 2002). Cerebrolysin increases the efficiency of energy metabolism in the brain, reduces the neurotoxic effects of drugs and prevents neuronal death. It is applied parenterally. For drug addicts, it is most advisable to administer Cerebrolysin intramuscularly and prescribe it during the period of remission, that is, two weeks after the onset of withdrawal symptoms. The optimal dose is 5-10 ml per day. Cerebrolysin helps to improve the concentration of attention in patients, they activate the processes of mental activity, and persistent positive emotions are formed.
During the period of remission, against the background of stabilization of the condition, patients may experience an exacerbation of craving for drugs, which in some cases manifests itself, as in the previous stages, in affective disorders, behavioral disorders or other mental disorders. In such cases, it is necessary to prescribe psychotropic drugs appropriate to the mental state of the patient: long-acting or short-acting antipsychotics, antidepressants. During this period, it is also recommended to carry out restorative therapy, including, in particular, nootropic drugs and the aforementioned cerebrolysin. You can use acupuncture, various methods of physiotherapy, taking into account individual indications and contraindications.
A very important step in the treatment of drug addiction is anti-relapse maintenance therapy. It is aimed at preventing the breakdown or relapse of the disease. The duration and quality of remission largely depends on this stage of the therapeutic process. It is very important to determine the factors that accompanied previous relapses of the disease, and the main clinical manifestations of mental dependence at this stage.
When using drugs of the opium group, an antagonist of opium receptors – naltrexone (naltrexone hydrochloride) – or its analogues – antaxon, revia, is used as a specific pathogenetic anti-relapse therapy.
The pharmacological mechanism of action of naltrexone hydrochloride is the complete blockade of opium receptors, as a result of which opiates coming from outside cannot bind to receptors and do not cause the effects characteristic of opium intoxication. However, therapy with naltrexone is possible only after complete relief of the withdrawal syndrome, since otherwise, patients may develop pronounced signs of withdrawal syndrome. After oral administration, naltrexone is rapidly and completely absorbed, and its maximum concentration in blood plasma is reached after 45 minutes and lasts up to 4. 5 hours. The drug is active within a day from the moment of its administration. A necessary condition for treatment with naltrexone is that at least 10 days must have passed since the last use of opiate group drugs, i.e. the body must be “free” from opiates. Before prescribing naltrexone, a test with a short-acting opiate antagonist, naloxone, can be performed to make sure that there are no drugs in the body. The optimal technique for conducting such a test is as follows: naloxone hydrochloride is administered intramuscularly or subcutaneously at a dose of 0.4-0.8 mg. If 10-15 minutes after the administration of naloxone, rudimentary signs of withdrawal symptoms appear: weakness, lability of affect, increased sensitivity to external stimuli, hyperhidrosis, intestinal spasms, yawning, unexpressed lacrimation, pain in the joints and muscles, mydriasis, tremor, etc. – prescribe therapy aimed at stopping these disorders. Then the injection of naloxone is repeated, and if it does not cause a deterioration in the condition, which indicates a complete relief of the withdrawal syndrome, patients are transferred to long-term treatment with naltrexone.
The weekly dose of naltrexone should be 350 mg. Maintenance therapy with naltrexone can be carried out according to the following schemes: one tablet (50 mg) per day daily or the first week of therapy – one tablet (50 mg) per day; in the future – twice a week – two tablets (100 mg), once – three tablets (150 mg).
As a rule, therapy with naltrexone is started in a hospital after relief of withdrawal symptoms and recovery of somatic and mental disorders, approximately one week before discharge. This is necessary in order to identify possible side effects and, if necessary, stop them in a hospital setting.
The first dose is 0.5 tablets (25 mg per day). If no side effects are noted, the next daily dose is 50 mg. The course of treatment with naltrexone is up to 180 days or more. Patients are warned that when taking drugs of the opiate group against the background of the action of naltrexone, they will not experience their euphoric effect, and if the dose of the drug is increased in order to get euphoria, an overdose may occur.
At the beginning of therapy, the following side effects may occur: redness of the skin, chills, weakness. These effects can be explained by the individual sensitivity of patients and insufficient detoxification. Usually these phenomena disappear with continued therapy. It should be noted that with alcohol overdose during naltrexone therapy, orthostatic collapses may occur.
It should be noted that in some patients, during treatment with naltrexone, various psychopathological disorders can be observed that characterize the primary pathological craving for drugs. This requires the addition of additional psychotropic drugs to naltrexone therapy: with the appearance of affective disorders – antidepressants and lithium salts; psychopathic – neuroleptics; asthenic – nootropics. After the relief of this symptomatology, these psychotropic drugs are canceled.
Thus, naltrexone can be used for anti-relapse treatment of patients with opium addiction as an opium receptor blocker. Side effects arising from the use of naltrexone (chills, weakness, etc.) are not an obstacle to its widespread introduction into clinical practice.
For patients with mental and physical dependence on drugs that have a psychostimulating effect (cocaine, amphetamine-like substances, ephedron, pervitin, etc.), there are also means of specific, pathogenetically substantiated anti-relapse therapy aimed at stopping mental dependence on drugs. One such remedy is bromocriptine (parlodel) (K. E. Voronin, 1993). It is known that with the simultaneous withdrawal of the drug, the appearance of such symptoms as anergy, depression, irritability, drowsiness is noted. After relief of withdrawal symptoms, treatment with bromocriptine continues at doses of 1.0-1.25 mg orally per day for several months to prevent the possible actualization of a pathological craving for the drug.
The effectiveness of bromocriptine is due to the elimination of dopamine depletion, which is the biological basis of mental and physical dependence. Pathogenetically substantiated long-term use of bromocriptine in patients with drug addiction caused by the use of psychostimulants can be considered a fairly effective anti-relapse therapy.
In addition to specific treatment programs used for the treatment of mental dependence in the process of long-term anti-relapse treatment, the entire spectrum of psychotropic drugs (neuroleptics, antidepressants, tranquilizers, nootropics, lithium salts, etc.) is widely used. In this case, it is necessary to follow the basic principle of psychopharmacology – the choice of drugs depends on the clinical and psychopathological picture of the syndrome to be stopped.
So, if the actualization of the primary pathological craving for drugs is characterized by a persistent periodicity with a gradual or sudden onset of affective disorders, lithium salts with the addition of antidepressants, if necessary, are the treatment of choice. Lithium carbonate is used 0.6-0.9g per day, lithium oxybutyrate – 1. 0-1.5 g per day, mikalit (microencapsulated salt of lithium carbonate) – two to three capsules (0.8-1.2 g of lithium carbonate) per day, litonite – 300-400 mg. Courses of treatment with these doses range from three to 12 months or more. With the predominance of asthenic disorders, nootropic drugs, cerebrolysin can be prescribed. Depending on the presence of affective and psychopathic disorders in the structure of mental dependence, neuroleptics and antidepressants are used. If necessary, if there are symptoms such as anxiety, fear, anxiety in the structure of mental dependence, benzodiazepine tranquilizers are prescribed.
In addition, as the data of clinical and follow-up observation show, in some cases, during the period of remission, there may be acute “flashes” of the actualization of a pathological craving for drugs. They can be regarded as vestiges of paroxysms of convulsive states. This makes it expedient to use anticonvulsants – carbamazepine (tegretol, finlepsin), as well as difenin or convulex.
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