Normotimics is a heterogeneous group of medications that are prescribed to stabilize mood in outpatient (supportive) psychiatry. Thymoisoleptics make it possible to prevent relapses and maintain remission over a long period of time in the treatment of, for example, bipolar affective disorder (BD), cyclothymia, schizophreniform disorder, schizoaffective psychosis, and moderate unipolar depression. Properly selected drugs in this group prevent or effectively smooth out mood swings, manic and depressive states.
The unique mechanism of action of mood stabilizers includes a double effect - they prevent or significantly mitigate affective phases and attacks of the schizoaffective structure, as well as depressive tendencies. This effect of lithium salts was first noticed in clinical practice in the first half of the 20th century. Some time later, in the mid-60s, Danish scientists Baastrup P. and Schou M. confirmed that lithium salts even out mood, while differing in their mechanism of action from antipsychotics and antidepressants. The discovery made it possible to initiate a discussion about the creation of a new group of drugs - mood stabilizers.
The final interest in drugs of this group arose in the late 70s, when active research began on the mechanisms of action of lithium salts, the search for analogues with desired properties, with less pronounced non-core effects and pronounced thymoisoleptic properties. In the late 80s, based on accumulated clinical experience and research results, the group of mood stabilizers began to include some anticonvulsants, antipsychotics, and tranquilizers with thymoleptic effects.
Classification of mood stabilizers
The International Anatomical Therapeutic Chemical Classification of Drugs (ATX) does not have a separate section for mood-boosting drugs. However, the classification indicates the normothimic properties of specific drugs, which, however, corresponds to the logic of its structure - according to the action profile.
Classification of mood stabilizers by chemical structure includes:
- lithium salts (carbonate, gluconate, sulfate, chloride, citrate, hydroxybutyrate, long-acting lithium preparations);
- carbamazepine derivatives;
- valproic acid derivatives;
- calcium channel blockers;
- some atypical antipsychotics;
- some benzodiazepine tranquilizers.
The phenomenon of amygdalar kindling
The presented groups consist of drugs with an anticonvulsant effect, which have a calming, mood-stabilizing effect. Their use in the psychiatry of reversible and borderline disorders is explained by a neurobiological hypothesis - the phenomenon of amygdala kindling. The hypothesis reflects ideas about the occurrence of epileptic seizures, associated, in particular, with the impact of psychological stimuli on the amygdala and limbic system of the brain. Their irritation at an individual superthreshold level, caused by emotional disturbances restrained and suppressed by a person, becomes the cause of epileptic seizures. Therefore, drugs of this group are effective for stopping not only convulsive activity, but also the underlying biochemical-psycho-emotional pathology, which causes a response from the same brain structures.
Rice. 1. One of the most complete classifications of mood stabilizers.
Introduction
Normotimics (mood stabilizers, thymoisoleptics) are a group of drugs that stabilize pathological affective fluctuations (mainly depressive and manic syndromes, or the so-called mixed states, to a lesser extent aggressiveness, irritability, impulsivity) in various mental disorders. This mainly applies to bipolar disorders (bipolar affective disorder, major depressive disorder, recurrent depressive disorder, schizoaffective disorder, etc.). According to the international anatomical-therapeutic-chemical classification (hereinafter referred to as ATC), recommended by the World Health Organization (WHO), there is no separate group of drugs such as “normotimics”. However, they all belong to group “N” (drugs for the treatment of diseases of the nervous system), their representatives belong to different subgroups; lithium from subgroup N05AN (antipsychotic drugs) of group N05 “Psycholeptics” [1], valproic acid, carbamazepine, lamotrigine - from group N03A (“Antiepileptic drugs”). In the countries of Western Europe and the USA, the above drugs are called mood stabilizers (English: “mood stabilizer”, less often “antimanic agents”), in Russia the generally accepted name for them is “normotimics”. Of all the existing mood stabilizers that are officially registered for use in Russia (according to the State Register of Medicines) [2], four drugs are known, not counting drugs from other groups (for example, some atypical antipsychotics), so further we will talk exclusively about them. All of the mood stabilizers listed above have a similar effect, which is mainly aimed at sodium channels (mainly their blockade) in the membranes of neurons of the central nervous system (hereinafter referred to as the CNS). This achieves a decrease in the release of norepinephrine [3], an increase in the synthesis of serotonin [3, 4, 5, 10, 11, 12], a decrease in dopamine neurotransmission [6], an increase in GABA levels [7–9], modulation and decrease in glutamate levels [6] , neuroplastic [15, 16] and neuroprotective effects [6, 13, 14].
Mechanism of action of mood stabilizers
The mechanism of action of mood stabilizers has been studied quite well. However, the psychobiological effects that occur when taking mood stabilizers have, indeed, been virtually unstudied. Modern research on thymoisoleptics aims to fill the missing knowledge about drugs in this group, focusing on the study of the following processes:
- on the concomitant biochemistry of neurotransmitters that occurs against the background of the course of target diseases;
- on processes at the cellular level (for example, on the interaction of the ligand with receptors, proteins and second messengers);
- on the interaction of neurotransmitter systems with neurotransmitters;
- on circadian rhythms in the presence of specific psychopathology;
- on the genetic factor (on the role of heredity).
It is known that the therapeutic mechanism of action of mood stabilizers is associated with the effect on neurotransmitters - cholinergic, catecholaminergic, indolaminergic and the GABA system. In particular, the latest research indicates the presence of biochemical processes on post- and preneuronal receptors, post-receptor activity of the above neurotransmitters.
Rice. 2. The mechanism of action of mood stabilizers.
Cholinergic system
In affective disorders, changes in the cholinergic-adrenergic system are observed. For example, in manic states, cholinergic activity decreases relative to noradrenergic activity, and in depressive states, vice versa. Research shows that some mood stabilizers are able to equalize the concentration of choline in red blood cells, thereby achieving a therapeutic effect.
Catecholaminergic system
Some mood stabilizers reduce the level of thyroid hormone and dopamine, which can increase the activity of the catecholaminergic system, which is the cause of manic states. In particular, this mechanism of action of mood stabilizers is confirmed by studies that note an increase in thyroid activity during the development of manic states and its decrease during recovery.
Indolamines
The effects of some mood stabilizers on indoleamine neurotransmitters increase serotonin levels through agonism at postsynaptic serotonergic receptors and by promoting tryptophan reuptake.
Gamma-aminobutyric acid (GABA)
Gamma-aminobutyric acid (GABA) is not only the main inhibitory neurotransmitter of the central nervous system, but also an inhibitor of neurotransmitters. Some mood stabilizers are able to increase the level of GABA, which in turn evens out the imbalance of neurotransmitters, providing a therapeutic effect.
Unique effects of mood stabilizers
In addition to the therapeutic effect exerted through their influence on neurotransmitter systems, mood stabilizers, in particular, act on opiate and benzodiazepine receptors and suppress the activation of adenylate cyclase of cyclic adenosine and guanine monophosphates. Therefore, the mechanism of action of mood stabilizers determines the wide range of use of drugs in this group in almost all areas of medicine.
The variety of biochemical processes stimulated during treatment with mood stabilizers is still of interest to researchers - various hypotheses are being tested that try to explain their unique therapeutic effect, and new ones are being put forward. In clinical practice, this implies the responsibility of doctors when prescribing drugs of this group, especially during long-term treatment.
In addition to the wide range of use of mood stabilizers, drugs in this group exhibit another common effect that has important clinical significance - smoothing of circadian fluctuations. Unlike other psychotropic drugs, mood stabilizers normalize ri, for example, in the treatment of manic states, as well as in the process of preventive therapy.
Rice. 3. Circadian rhythm.
Indications for the use of mood stabilizers
In clinical practice, when prescribing mood stabilizers, they are guided by the degree of severity of the necessary therapeutic effects of a particular drug. In particular, the characteristics of the course of the disease, health status and lifestyle of the patient are taken into account. And although the therapeutic mechanism of action of all thymoisoleptics is reduced to mood stabilization, specific indications for prescribing mood stabilizers still exist (below will be given the features of the therapeutic effects of some drugs in terms of prescription in the treatment of target psychopathology).
Lithium
Lithium salts are the most famous representatives of this group of drugs. Indications for the use of lithium-based mood stabilizers include:
- bipolar affective disorder;
- severe forms of depression;
- resistant forms of depression;
- affective psychoses;
- other affective disorders.
In particular, lithium preparations are used in the treatment of mood disorders in chronic alcoholism; in dermatology - for viral infections, seborrheic dermatitis, mycoses; in neurology - a positive therapeutic effect is noted in the treatment of amyotrophic lateral sclerosis (degenerative processes are slowed down).
Valproic acid
Valproic acid has a pronounced antimanic effect. The antidepressant effect manifests itself, as a rule, in the treatment of mixed conditions, when depression occurs in parallel with mania.
Preparations based on valproic acid are used in the clinic for the following mental disorders:
- bipolar affective disorder;
- schizophrenia (in complex psychopharmacotherapy);
- dopamine dysregulation syndrome;
- tension headaches.
Valproic acid drugs are first-line drugs in the treatment of epilepsy (tonic-clonic seizures, myoclonic seizures, absence of seizures).
Carbamazepine
Carbamazepine is a universal mood stabilizer due to its weak antimanic effect and dominant anti-anxiety and antidepressant effect. The drug is able to improve mood, promote mental activity, smooth out hot temper and irritability. Typically, the indication for its use is depression, accompanied by anxiety, lethargy, loss of strength and tearfulness.
In addition, carbamazepine is the first-line drug for the treatment of trigeminal neuralgia; in narcology - in the treatment of withdrawal states accompanied by convulsions, vegetative and mental disorders.
Oxcarbamazepine
Oxcarbamazepine has a weak sedative effect and a pronounced antimanic effect, allowing you to cope with tremor. As a rule, it is prescribed in the presence of manic phases in the structure of depressive states, bipolar affective disorder.
Lamotrigine
Lamotrigine is effective in the treatment of bipolar affective disorder type I with severe depressive phases; The antimanic effect is quite weak. Used in combination with SSRIs to treat depersonalization-derealization syndrome, borderline personality disorder, schizoaffective disorder, resistant OCD, and hallucinogen-induced disorders.
Rice. 4. The use of mood stabilizers in the treatment of mental disorders with manic states.
Application tactics
Taking into account officially registered instructions for the use of drugs [2], the following tactics for the use of mood stabilizers are recommended in Russian clinical practice. Outpatient tactics. Normotimics can be used: a) for the treatment and prevention of affective spectrum disorders as a basic drug intended for long-term use (start with small doses, gradually increasing them to medium therapeutic doses), as well as as part of complex therapy for concomitant psychiatric pathologies (anxiolytics, antidepressants, antipsychotics) if necessary; b) to strengthen (augment) basic therapy (antidepressive, antipsychotic, anti-anxiety, etc.) for various disorders in the structure of which there are significant affective disorders (start with small doses of mood stabilizers, gradually increasing them to medium therapeutic doses). Stationary tactics. Allows you to quickly relieve severe symptoms (manic, depressive, mixed) in disorders predominantly of the bipolar spectrum. Normotimics are prescribed in average therapeutic doses or slightly higher as basic therapy for a long period, supplemented with drugs from other groups (anxiolytics, antipsychotics, antidepressants, etc.). Thus strengthening the effect on psychopathological symptoms, their dosage is subsequently first reduced, and as the condition stabilizes, if possible, canceled. It should be noted that for bipolar spectrum disorders after stabilization of the condition and achievement of drug remission (both in outpatient and inpatient treatment). Drugs with normothimic activity currently registered in Russia are presented in Table. 5 (with the exception of trade names of the form “INN”, “INN - manufacturer” or features of the dosage form) it is not clear what is meant by this [2]. In addition to the drug group, its price and availability are important for clinical practice (legislative regulation of drug prescription, policy of pharmacy chains). These parameters are largely subject to change (price changes, legislative practice of the national health care system), therefore the final decision on prescribing a particular drug is made by the attending physician, taking into account the indications, contraindications, clinical profile of the drug, its pharmacodynamics, pharmacokinetics, individual characteristics of the patient and the specified above factors. When prescribing a mood stabilizer, it is necessary to take into account the age restrictions of the drug, its effect on driving vehicles and activities requiring increased concentration, as well as the possibility of use during pregnancy and lactation in accordance with the official instructions for drugs * (Table 6 *) [2 ].
Side effects of mood stabilizers
To avoid side effects of mood stabilizers, it is necessary to select the minimum effective dosage under the supervision of the attending physician. If non-core actions occur, the attending physician will correct the treatment. Refusal of treatment or independent adjustment of the dosage of the drug taken is unacceptable.
The main side effects of mood stabilizers include:
- nausea;
- drowsiness;
- lethargy;
- muscle weakness;
- slurred speech;
- dizziness;
- double vision.
Drug selection stage
The reaction of patients to taking mood stabilizers is individual. It depends, for example, on the characteristics of the course of the disease and state of health. At the stage of drug selection and dosage, short-term (reversible) side effects of mood stabilizers may occur. Therefore, the patient needs to note unusual sensations and conditions and promptly notify the attending physician about them, for example:
- about daytime sleepiness;
- about mild muscle weakness;
- about difficulty concentrating.
A personalized approach to drug selection, associated with the occurrence of side effects of mood stabilizers, should not become a reason for refusing treatment. On the contrary, a correctly selected mood stabilizer will allow you to avoid the increased intensity of non-core effects of drugs from other groups.
Depakine® chrono
Before starting to use the drug and periodically during the first 6 months of treatment, especially in patients at risk of developing liver damage, liver function tests should be performed.
As with the use of most antiepileptic drugs, when using valproic acid, a slight increase in the activity of “liver” transaminases is possible, especially at the beginning of treatment, which occurs without clinical manifestations and is transient. In such patients, it is necessary to conduct a more thorough study of biological parameters, including the prothrombin index. It may be necessary to adjust the dose of the drug, and, if necessary, repeat clinical and laboratory examination.
Before starting therapy or before surgery, as well as in the event of spontaneous occurrence of subcutaneous hematomas or bleeding, it is recommended to determine the bleeding time and the number of formed elements in the peripheral blood, including platelets.
Severe liver damage
Predisposing factors
Isolated cases of severe liver damage, sometimes fatal, have been described. Clinical experience shows that patients taking multiple antiepileptic drugs at the same time and patients taking salicylates at the same time (since salicylates are metabolized through the same metabolic pathway as valproic acid) are at risk.
Suspicion of liver damage
For early diagnosis of liver damage, clinical observation of patients is mandatory. In particular, you should pay attention to the following symptoms that may precede the onset of jaundice, especially in patients at risk:
- nonspecific symptoms, especially those that began suddenly, such as asthenia, anorexia, lethargy, drowsiness, which are sometimes accompanied by repeated vomiting and abdominal pain;
- resumption of seizures in patients with epilepsy.
Patients or their family members (when using the drug in pediatric patients) should be warned that they should immediately report the occurrence of any of these symptoms to their doctor. Patients should immediately undergo clinical examination and laboratory testing of liver function tests.
Revealing
Liver function tests should be performed before starting treatment and then periodically during the first 6 months of treatment. Among conventional studies, the most informative are studies reflecting the state of the protein-synthetic function of the liver, especially the determination of the prothrombin index. Confirmation of deviation from the norm of the prothrombin index in the direction of its decrease, especially in combination with deviations from the norm of other laboratory parameters (a significant decrease in the content of fibrinogen and blood clotting factors, an increase in the concentration of bilirubin and an increase in the activity of “liver” transaminases), as well as the appearance of other symptoms indicating for liver damage, requires discontinuation of the drug. As a precaution, if patients were taking salicylates concomitantly, their use should also be discontinued.
Pancreatitis
There are rare reported cases of severe forms of pancreatitis in children and adults, which developed regardless of age and duration of treatment. Several cases of hemorrhagic pancreatitis have been observed with rapid progression of the disease from the first symptoms to death.
Children are at increased risk of developing pancreatitis, and this risk decreases with increasing age of the child. Risk factors for developing pancreatitis may include severe seizures, neurological disorders, or anticonvulsant therapy. Liver failure combined with pancreatitis increases the risk of death.
If severe abdominal pain, nausea, vomiting and/or anorexia occur, patients should be evaluated immediately. If pancreatitis is confirmed, in particular, with increased activity of pancreatic enzymes in the blood, the use of valproic acid should be discontinued and appropriate treatment should be started.
Suicidal thoughts and attempts
Suicidal ideation and suicide attempts have been reported in patients taking antiepileptic drugs for some indications. A meta-analysis of randomized placebo-controlled trials of antiepileptic drugs also showed a 0.19% increase in the risk of suicidal ideation and suicide attempts in all patients taking antiepileptic drugs (including a 0.24% increase in this risk in patients taking antiepileptic drugs for epilepsy), compared with their frequency in patients taking placebo. The mechanism of this effect is unknown.
Therefore, patients taking the drug should be constantly monitored for suicidal thoughts and suicide attempts, and if they occur, appropriate treatment should be provided. Patients and their caregivers are advised to immediately consult a physician if they experience suicidal thoughts or suicide attempts.
Carbapenems
The simultaneous use of carbapenems is not recommended (see section “Interaction with other drugs”, “With caution”).
Patients with established or suspected mitochondrial diseases Valproic acid may initiate or aggravate the manifestations of the patient's existing mitochondrial diseases caused by mutations in mitochondrial DNA, as well as in the nuclear gene encoding the mitochondrial enzyme γ-polymerase (POLG). In particular, in patients with congenital neurometabolic syndromes caused by mutations in the gene encoding γ-polymerase (POLG), such as patients with Alpers-Huttenlocher syndrome, valproic acid is associated with a higher incidence of acute liver failure and liver-related deaths. outcomes. The presence of diseases caused by defects in γ-polymerase can be assumed in patients with a family history or symptoms of such diseases, including encephalopathy of unknown origin, refractory epilepsy (focal, myoclonic), status epilepticus, mental and physical retardation, psychomotor regression, axonal sensorimotor neuropathy, myopathy, cerebellar ataxia, ophthalmoplegia or complicated migraine with visual (occipital) aura. In accordance with current clinical practice, testing for mutations in the polymerase γ gene (POLG) should be performed to diagnose such diseases (see section "Contraindications").
Paradoxical increase in the frequency and severity of seizures (including the development of status epilepticus) or the emergence of new types of seizures
As with other antiepileptic drugs, when taking valproic acid, instead of improvement, some patients experienced a reversible increase in the frequency and severity of seizures (including the development of status epilepticus) or the appearance of new types of seizures. If seizures worsen, patients should immediately consult their doctor (see section "Side effects").
Female children and adolescents, women of childbearing potential and pregnant women
Pregnancy Prevention Program
Valproic acid has a high teratogenic effect; the use of valproic acid leads to a high risk of congenital malformations and developmental disorders of the central nervous system in the fetus.
The use of valproic acid is contraindicated:
- during pregnancy for epilepsy, except in cases of absence of alternative treatment methods (see sections “Special instructions”, “Use during pregnancy and during breastfeeding”);
— during pregnancy in the treatment and prevention of bipolar affective disorders;
- in women of childbearing potential, unless all the conditions of the Pregnancy Prevention Program are met (see sections “Special Instructions”, “Use during Pregnancy and Breastfeeding”).
When prescribing drugs containing valproic acid, you must:
— conduct an individual assessment of the circumstances of prescribing the drug in each individual case, discuss possible methods of therapy and make sure that the patient understands the potential risks and the need for measures taken to minimize them;
— make sure that the patient has childbearing potential;
— make sure that the patient understands the nature and magnitude of the risks of using valproic acid during pregnancy, in particular, the risks of teratogenic effects, as well as the risks of disorders of the mental and physical development of the child;
— make sure that the patient understands the need to conduct a pregnancy test before starting and during treatment;
- explain the necessary methods of contraception, make sure that the patient uses reliable methods of contraception continuously during treatment with drugs containing valproic acid;
— make sure that the patient understands the need to regularly contact a specialist in the treatment of epilepsy and bipolar affective disorders (at least once a year) to re-analyze the prescribed therapy;
- make sure that the patient understands the need to contact her doctor if she is planning a pregnancy in order to promptly assess the possibility of switching to alternative therapy before stopping the use of contraception;
- inform about the need for immediate consultation with your doctor if you suspect pregnancy;
— ensure that the patient has received all the necessary explanations about the risks and necessary precautions.
The above information is also relevant for women who are not currently sexually active, unless the attending physician is satisfied that there is no childbearing potential.
Female pediatric patients
When prescribing drugs containing valproic acid, you must:
— make sure that female pediatric patients/their legal representatives understand the need to consult with their doctor upon the onset of menarche;
— ensure that female pediatric patients who have reached menarche, or their legal representatives, receive detailed information about the risks of congenital malformations and disorders of the central nervous system in the fetus.
The treating physician should annually re-evaluate the prescribed valproic acid therapy and evaluate the possibility of prescribing alternative therapy. If drugs containing valproic acid are the treatment of choice, it is necessary to ensure that reliable methods of contraception are used and that the terms of the Pregnancy Prevention Program are followed. Before puberty, the possibility of switching patients to alternative treatment methods should be constantly considered.
Pregnancy test
Before starting treatment with drugs containing valproic acid, it is necessary to exclude pregnancy. Therapy with drugs containing valproic acid cannot be prescribed to women of childbearing potential unless a negative pregnancy test (pregnancy blood test) has been confirmed by a health care professional to prevent the drug from being prescribed during pregnancy.
Contraception methods
Female patients of childbearing potential who are prescribed therapy with drugs containing valproic acid should use reliable methods of contraception continuously throughout the entire treatment period.
Female patients of childbearing potential should be provided with detailed information about methods of preventing pregnancy, and such patients may also seek advice from their physician if they are not using a reliable method of contraception.
You must use at least one reliable method of contraception (preferably simultaneously with methods such as an intrauterine system or implant) or two complementary methods of contraception, including barrier methods. When prescribing a contraceptive method to a patient, it is necessary to take an individualized approach and discuss all possible contraceptive options with the patient to ensure that the patient adheres to and adheres to the regimen. In case of amenorrhea, the patient should also be warned about the use of effective methods of contraception.
Annual analysis of prescribed therapy
At least once a year, the treating physician should evaluate whether medications containing valproic acid are the treatment of choice. The risks associated with therapy should be discussed when prescribing the drug and at each annual review of the prescribed therapy, and ensure that the patient understands all risks.
Planning a pregnancy
If a patient is planning a pregnancy, a specialist in the treatment of epilepsy and bipolar affective disorder should evaluate therapy with drugs containing valproic acid and consider alternative therapy. Every effort should be made to switch the patient from therapy with drugs containing valproic acid before conception and until contraception is discontinued (see section “Use during pregnancy and breastfeeding”). If alternative therapy is not available, the patient should be advised of the risks associated with the use of drugs containing valproic acid for the unborn child to help make an informed decision about family planning.
What to do if you become pregnant?
If you become pregnant, you should contact your healthcare provider immediately to evaluate your treatment and consider alternative therapy.
The health worker must ensure that:
— patients understand all the risks described above;
— patients received recommendations not to stop therapy with valproic acid and to immediately contact their doctor when planning pregnancy.
Concomitant use with estrogen-containing drugs
Valproic acid does not reduce the therapeutic effectiveness of hormonal contraceptives. However, drugs containing estrogen, including estrogen-containing hormonal contraceptives, may increase the clearance of valproic acid, which may lead to a decrease in its serum concentration and, consequently, a decrease in its effectiveness. It is necessary to monitor the concentration of valproic acid in the blood serum and clinical effectiveness (seizure control and mood control) when prescribing or discontinuing estrogen-containing drugs (see section "Interaction with other drugs").
Kidney failure
It may be necessary to reduce the dose of valproic acid due to an increase in the concentration of its free fraction in the blood serum. If it is impossible to monitor plasma concentrations of valproic acid, the dose of the drug should be adjusted based on clinical observation of the patient.
Enzyme deficiency of the carbamide cycle (urea cycle)
If an enzymatic deficiency of the carbamide cycle is suspected, the use of valproic acid is contraindicated. In such patients, several cases of hyperammonemia with the development of stupor or coma have been described. In these cases, metabolic studies should be carried out before starting treatment with valproic acid (see section “Contraindications”).
In children with unexplained gastrointestinal symptoms (anorexia, vomiting, cases of cytolysis), a history of lethargy or coma, with mental retardation or a family history of death of a newborn or child, metabolic studies should be carried out before starting treatment with valproic acid drugs, in particular determination of ammonemia (presence of ammonia and its compounds in the blood) on an empty stomach and after meals (see section “Contraindications”).
Patients with systemic lupus erythematosus
Although immune dysfunction is extremely rare during treatment with valproic acid, the potential benefits of their use must be weighed against the potential risks when administered to patients with systemic lupus erythematosus.
Weight gain
Patients should be warned about the risk of weight gain at the beginning of treatment and the need to take dietary measures to minimize this phenomenon.
Patients with diabetes mellitus
Given the possibility of adverse effects of valproic acid on the pancreas, when using the drug in patients with diabetes mellitus, blood glucose concentrations should be carefully monitored. When testing urine for the presence of ketone bodies in patients with diabetes, it is possible to obtain false-positive results, since valproic acid is excreted partially by the kidneys in the form of ketone bodies.
Patients infected with human immunodeficiency virus (HIV)
in vitro studies
Valproic acid has been found to stimulate HIV replication under certain experimental conditions.
The clinical significance of this fact is unknown. In addition, the significance of data obtained from in vitro
for patients receiving maximally suppressive antiretroviral therapy has not been established. However, these data should be taken into account when interpreting the results of continuous viral load monitoring in HIV-infected patients taking valproic acid.
Patients with existing carnitine palmitoyltransferase (CPT) type II deficiency:
Patients with existing CPT type II deficiency should be warned of the higher risk of developing rhabdomyolysis when taking valproic acid.
Ethanol
: During treatment with valproic acid, ethanol consumption is not recommended.
Other special instructions
The inert matrix of the drug (extended release drug), due to the nature of its excipients, is not absorbed in the gastrointestinal tract; after the release of the active substances, the inert matrix is excreted by the intestines.
List of mood stabilizers
Currently, the list of mood stabilizers may include not only names with a combined antidepressant and antimanic effect, but also only those with a mood-stabilizing effect (for example, lamotrigine does not have antimanic activity). In addition, the additional properties of some mood stabilizers expand the range of the group’s therapeutic profile, making it possible to prescribe such drugs in the treatment of mental disorders that include anxiety and panic symptoms.
Mineral salts
The list of mood stabilizer drugs includes various names, the active ingredient of which is:
- lithium carbonate;
- lithium gluconate;
- lithium chloride;
- lithium citrate;
- lithium oxybate;
- long-acting forms of lithium;
- rubidium chloride;
- Cesium chloride.
Anticonvulsants with normothimic activity
Anticonvulsant medications from the list of mood stabilizers include:
- Carbamazepine;
- Oxcarbazepine;
- Valproic acid;
- Lamotrigine;
- Gabapentin;
- Levetiracetam.
Atypical antipsychotics
Atypical antipsychotics belonging to the list of mood stabilizers are represented by the following names:
- Aripiprazole;
- Asenapine;
- Risperidone;
- Olanzapine;
- Quetiapine;
- Clozapine.
Calcium antagonists
Calcium antagonists are:
- Verapamil;
- Nifedipine;
- Nimodipine.
Thyroid hormones
As a rule, thyroid hormones are included in the list of mood stabilizers on the principle of additional therapy when discontinuation of antidepressants is required:
- Triiodothyronine;
- L-thyroxine.
List of used literature
1. Mazo G.E. “Normotimiki in the treatment of treatment-resistant depression: anti-resistant therapy or influence on latent bipolarity?”
2. Marilov V.V., Sologub M.B. “Comparative effectiveness of mood stabilizers in complex therapy of bulimia nervosa.”
3. Malin D.I. "Drug interactions of drugs used in psychiatric practice."
4. Aleksandrovsky Yu.A. "Rational pharmacotherapy in psychiatric practice: a guide for practitioners."
5. Maslov K.A. “Normotimiki in Russia in modern clinical practice of a psychiatrist.”
6. Arana D., Rosenbaum D.F. "Guide to psychopharmacotherapy."
7. Amir O. “Normotimiki.”
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A Brief History of Normotimics
The first and main representatives of the group of normotimics were lithium preparations, known since ancient times, but their normotimic effect was discovered only in the 19th century [17]. They have been used in modern clinical practice since 1970 [18], when, after the ban on lithium in 1949, it returned to the arsenal of doctors. Almost simultaneously with it, the antiepileptic drug carbamazepine enters clinical practice (since 1962, and as a mood stabilizer - since 1971) [19]. Then came the turn of valproic acid drugs (in clinical practice since 1967, as a mood stabilizer since 1995) [20, 23]. The latest and youngest mood stabilizer is currently lamotrigine (in clinical practice since 1991, as a mood stabilizer since 2003) [21, 22].
Cost of treatment in our clinic
| Service | Price | |
| Ambulatory treatment | ||
| Psychiatrist consultation | 4 500 ₽ | |
| Consultation with a psychotherapist | 4 500 ₽ | |
| Psychodiagnostics extended | 7 000 ₽ | |
| Consultation with a psychiatrist at home | 6 000 ₽ | |
| Treatment in hospital | ||
| Delivery to hospital | For free | |
| Standard room | 7 700 ₽ | |
| 3-bed superior room | 10 600 ₽ | |
| 2-bed superior room | 13 700 ₽ | |
| 1 local VIP chamber | 19 000 ₽ | |
| Doctor's appointment 2 weeks after discharge | For free | |
