Drugs for the treatment of cognitive disorders
To correct memory and thinking, including in Alzheimer's disease, agents affecting specific receptors and neuronal metabolism are used. The primary cause of cognitive decline in Alzheimer's disease is a shortage of the neurotransmitter acetylcholine.
- Replenishment of acetylcholine deficiency: precursors of this substance are used, for example, choline alfoscerate.
- Cholinesterase blockade: the enzyme that breaks down acetylcholine is inhibited by special inhibitors. Galantamine, donepezil, rivastigmine, and ipidacrine act selectively on the brain. Non-selective agents (neostigmine methylsulfate, pilocarpine) frequently cause severe peripheral side effects, such as bronchospasm, slowed pulse, seizures, and diarrhea.
- Protection of neurons from toxicity: the drug memantine blocks glutamate receptors, preventing cell death from excessive excitation (excitotoxicity).
- Antioxidant therapy: to halt lipid peroxidation in organic brain damage, vitamin E, meldonium, or ethylmethylhydroxypyridine succinate is prescribed.
In addition, there are peptide drugs (e.g., semax, which is an ACTH fragment) administered intranasally, ensuring rapid delivery to the brain without systemic adverse reactions.
Mood stabilizers
Mood stabilizers are used to prevent sharp emotional fluctuations, treat manic states, and control aggression and suicidal tendencies in schizophrenia and bipolar disorder.
Lithium salts Lithium preparations effectively smooth out mood phases but have a narrow therapeutic window. This means that the difference between the therapeutic and toxic dose is extremely small. Patients require strict weekly monitoring of blood lithium levels:
- Prophylactic concentration: 0.6–0.9 mmol/L.
- Concentration in acute mania: up to 1.2 mmol/L.
Overdose manifests as tremor, polyuria, digestive disorders (diarrhea, nausea, metallic taste), headache, and thyroid dysfunction. To minimize concentration fluctuations, it is important to monitor fluid intake and use depot formulations of the drug.
Alternative agents If lithium is not suitable, the following are prescribed:
- Anticonvulsants: carbamazepine, valproates, topiramate. They have a broader therapeutic range and additional calming effects.
- Antipsychotics: olanzapine, risperidone, haloperidol. They help stabilize cyclic mood swings and manage mania.
Mechanisms of action of anticonvulsants
Pathological seizure activity occurs due to a disruption in the balance of inhibitory (GABA) and excitatory (glutamate) systems, as well as excessive intracellular accumulation of sodium ions.
Depending on their site of action, anticonvulsants are divided into the following groups:
- GABA-enhancing agents: receptor agonists (barbiturates, benzodiazepines) and GABA degradation blockers (gabapentin, valproates).
- Glutamate-reducing agents: lamotrigine.
- Sodium excretion stimulants: acetazolamide, phenytoin.
- Combined-action agents: topiramate.
- Agents with an unclear mechanism: levetiracetam (structurally close to nootropics).
Selection of an anticonvulsant depending on the type of seizure
Drug selection depends on the nature of the leading syndrome, the risk-benefit ratio, and pharmacokinetics. Preference is given to long-acting drugs or depot formulations of short-acting substances (e.g., retard formulations of carbamazepine or valproic acid) so that blood concentrations remain stable.
| Type of disorder | Drugs of choice |
|---|---|
| Universal agents | Valproates, topiramate, lamotrigine, levetiracetam |
| Major tonic-clonic seizures | Barbiturates, phenytoin, carbamazepine, acetazolamide |
| Absence seizures | Ethosuximide, benzodiazepines, trimethadione |
| Partial seizures | Carbamazepine, gabapentin, pregabalin, vigabatrin |
| Panic attacks | Benzodiazepines, pregabalin, carbamazepine |
Anticonvulsants are used not only for epilepsy, but also for the treatment of bipolar disorder, dysphoria, impulsive behavior, and non-epileptic paroxysms.
Treatment specifics and discontinuation rules
Successful treatment requires adherence to several strict rules:
- Continuity: medications are taken long-term, without omissions.
- Dose titration: therapy is always initiated at minimal dosages with subsequent slow increases until a therapeutic effect is achieved (the low and slow principle).
- Caution in the elderly: nootropic agents and antioxidants (memantine, mexidol, piracetam) can provoke anxiety and insomnia.
- Discontinuation rules: complete cessation of anticonvulsants is possible only if the patient has been seizure-free for at least three (ideally five) years. Dosage reduction is carried out extremely slowly and gradually.
Briefly: answers to topical questions
What are the absolute indications and methodology for electroconvulsive therapy in treatment-resistant depression?
Sources do not single out absolute indications for electroconvulsive therapy; the main indications include severe endogenous depressions and overcoming resistance in the pharmacotherapy of endogenous psychoses. Absolute contraindications are absent. The methodology includes two electrode placement options under muscle relaxants with mandatory EEG and ECG recording:
- Bilateral placement — characterized by higher efficacy and a lower total cumulative electrical dose, but increases the risk of cognitive impairment.
- Unilateral placement — considered safer, but somewhat less effective; the exposure exceeds the threshold by 2.5–6 times.
What cognitive side effects and complications does electroconvulsive therapy cause?
Electroconvulsive therapy can cause transient memory impairment and the development of amnestic syndrome. The risk of cognitive impairment is particularly high with bilateral electrode placement due to the narrow therapeutic window (the effective and safe dose exceeds the threshold by only 1.5–2.5 times). When using brief-pulse techniques, the probability of memory impairment is reduced to 1.4%.
How do the indications for selective versus non-selective cholinesterase inhibitors differ?
In Alzheimer's disease, sources indicate cholinesterase inhibitors from both groups. Non-selective cholinesterase inhibitors have a pronounced peripheral effect, including diarrhea, bradycardia, bronchospasm, seizures, and sialorrhea. Selective cholinesterase inhibitors acting on the central nervous system are the drugs of choice; these include ipidacrine, galantamine, rivastigmine, and donepezil.
Class and exam questions
Why are cholinesterase inhibitors prescribed for Alzheimer's disease?
The basis of memory disorders in this disease is a deficiency of the neurotransmitter acetylcholine. Cholinesterase inhibitors block the enzyme that breaks down acetylcholine, thereby increasing its concentration in the brain.
How to properly select the dosage of anticonvulsants?
The selection is always carried out according to the principle of gradual titration: treatment starts with a minimum dose and is increased very slowly until seizure control is achieved without pronounced side effects.
What to do if a patient is taking lithium preparations?
It is necessary to strictly monitor the water-salt balance and diuresis, and measure plasma lithium levels weekly, as the drug has a very narrow therapeutic index and easily causes intoxication.
What else to study on this topic
- Indirect nootropic-like action of psychostimulants and antidepressants
- Peripheral side effects of non-selective cholinesterase inhibitors
- Use of anticonvulsants in bipolar affective disorder
- Specifics of the pharmacokinetics of depot mood stabilizers
- Mechanism of excitotoxicity and the role of glutamate receptors
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