What is bipolar disorder, why is it so difficult to diagnose mania and hypomania , why taking lithium salts requires constant blood tests, and what is the main difference between a dietary supplement and a medicine with a similar composition .
Lithium enters the BAR – and the doctor tells them … This could be the beginning of an anecdote about a new drug with salts of this metal, which is offered in pharmacies as a Russian alternative to drugs for bipolar-affective disorder. Only psychiatrists are not laughing. Let’s figure out what’s the matter.
Two sides of the same coin
Lithium salts can be prescribed for bipolar disorder (BAD), episodes of mania and hypomania , and less commonly for major depressive disorder (although this indication is not approved by the US Food and Drug Administration, it has been prescribed worldwide since 1980 -x and confirm the results by clinical studies). What is BAR, against which drugs with lithium salts are in the first line of defense? Bipolar disorder is called bipolar disorder because the patient often has two “poles” of behavior: the depressive stage and the manic stage.
Everyone has heard about depression, and many are sure that they have experienced it more than once, even if we are talking about a brief decline in mood – no longer than a week or two. In reality, depression manifests itself not just as an attack of sadness and depression, but is also accompanied by apathy, loss of interest in all activities and pleasures, and lasts at least a month. With mania, the situation is even more fun – both literally and figuratively. Almost everyone, having heard this word, imagines a maniac or a patient from anecdotes who imagines himself Napoleon (the notorious megalomania). In reality, psychiatrists understand this term as an ecstatic, agitated state, constant euphoria and a very high mood for no reason. The thoughts of a man in the stage of mania run chaotically in a race with emotions, he gushes with ideas and can work hard, be unexpectedly assertive, unpredictable and irritable, often distracted. A similar mood can occur in a healthy person, but the fuse will only last for a few days. People with mania can be in this state for months.
The manic patient feels joyful, active and productive, and his self-esteem may be overestimated if he does not become exhausted or does not suffer from impulsive behavior. A weaker version of this condition is called hypomania , and a person may perceive it as normal, complaining only of periodic depression, and others may confuse him with an active extrovert. It is not surprising that even a psychiatrist finds it difficult to diagnose bipolar disorder immediately and distinguish it from unipolar depression (that is, without another “pole”), because not every patient analyzes and remembers his mood in sequence and in different months of life. Moreover, it never occurs to anyone to complain if the mood is upbeat and inspired. In the first type of bipolar disorder, depressive episodes (which are usually three times longer) alternate with manic episodes, in the second, periods of rise look like hypomania , but there are other varieties. One of the saddest is the mixed type, when heightened energy spills into a depressed mood. Unless there is no mania without depression with bipolar disorder: perhaps the body cannot withstand a constant life “on the rise” and lack of sleep.
Lithium has become one of the oldest drugs in bipolar disorder medicine. The use of salts of this metal against the symptoms of mental disorders began in the late 1940s in Australia (and even before they tried to treat gout, cancer and epilepsy, but did not succeed very much). All these years, he confidently holds positions without leaving the list of drugs recommended by the World Health Organization as the most effective, safe and cost-effective for use. In the acute stage of mania, according to clinical studies, lithium may be inferior to drugs from the antipsychotics group in terms of tolerance and effectiveness. But in the recommendations for bipolar disorder, it is ahead of even antidepressants, because the latter can provoke the transformation of depression into mania or a rapid change in episodes of both stages.
From what, from what
What are lithium-based drugs and how do they work? Lithium is an alkali metal, which means that it tends very strongly to chemical reactions (as a reducing agent). If a piece of iron can be put on the table and left, then metallic lithium is even stored in kerosene, otherwise it is immediately covered with a film of oxide and carbonate. Upon contact with moist skin and mucous membranes, it leaves chemical burns, as it begins to turn into alkali, taking oxygen and hydrogen from the water (the remaining hydrogen is released). Few would have thought of swallowing such a medicine. It is not surprising that lithium is used in medicine in the form of salts. Most often (and in Russia – no options) it is lithium carbonate – Li 2 CO 3 .
But recently, an alternative has emerged, which (to the outrage of psychiatrists) has begun to offer in pharmacies instead of the traditional Sedalit . This drug Normotim (the name directly refers to the drug group of normotimics , or mood stabilizers), which, in addition to lithium in the form of ascorbate (a salt of ascorbic acid, that is, in combination with vitamin C), also contains vitamins B1 and B2. Indeed, a lack of these vitamins can cause neurological damage (for example, Wernicke-Korsakoff syndrome). However, vitamins must be distinguished from drugs: if they “cure” something, then only their own shortage. On the other hand, the preparation contains approximately the daily intake of both vitamins for an adult man (1, 2), which is too little for a serious overdose, so they cannot do any harm.
Preparations with lithium salts can still be toxic to humans. Side effects include a decrease in the production of thyroid hormones ( hypothyroidism , which, which looks somewhat paradoxical, increases the likelihood of depression), diabetes insipidus (increased thirst and an increased amount of urine due to impaired thirst control functions in the hypothalamus, subsequent disruption of kidney function), poisoning … And this is not counting the frequent (more than 10% of patients), but less dangerous cases, when patients develop muscle weakness, dry mouth, nausea, their hands tremble and the ECG indicators change. Acne appears a little less often, hair deteriorates.
But that’s not all. The toxic amounts of lithium are close to the dosages prescribed for patients. Therefore, when prescribing such drugs, each doctor must individually select the dosage, monitoring the safe content of lithium salts in the blood. In blood plasma, the threshold of safe concentrations for adults is 1.2 mmol / l, and for children – 0.5-1 mmol / l.
Lithium at work
Since lithium salts have been used in the treatment of mental disorders since the middle of the last century, their effect on humans has been well studied. The mechanism of action of lithium is not well understood. It probably replaces sodium, its “neighbor” in the column in the periodic table of chemical elements. In healthy people, it does not cause euphoria, unlike many other drugs in psychiatry, the sale of which often has to be severely restricted. Lithium increases the production of serotonin, which is mistakenly called the “hormone of happiness” (but for all its many roles, it may actually be associated with depression). It can also interfere with the work of other signaling substances (for example, nitric oxide NO) and activate a pathway called mTOR . But how this affects mood is not known for certain.
On the other hand, this did not prevent physicians from conducting many clinical trials of drugs with lithium salts and learning about its effectiveness in different directions. For example, in acute mania (according to a review by the Cochrane Collaboration , which reviewed studies involving more than four thousand patients in total), lithium was more effective than placebo and topiramate (drugs for epilepsy) and, most likely, was in no way inferior to other normotimics and drugs from the group of antipsychotics ( except olanzapine and risperidone , but this is not certain).
The Cochrane Library is a database of the Cochrane Collaboration, an international non-profit organization that participates in the development of guidelines of the World Health Organization. The name of the organization comes from the name of its founder, 20th century Scottish medical scientist Archibald Cochrane , who advocated the need for evidence-based medicine and competent clinical trials and wrote the book “Effectiveness and Effectiveness: Accidental Reflections on Health Care.” Medical scientists and pharmacists consider the Cochrane Database as one of the most authoritative sources of such information: the publications included in it have been selected by the standards of evidence-based medicine and report the results of randomized, double-blind, placebo-controlled clinical trials.
In general, lithium is recognized as an effective and safe drug for long-term use against bipolar disorder (although there are clearly fewer data on the unipolar variant of the disorder). It was also not clear to the reviewers (published in 2001) how well it helps prevent suicide and whether it is better than antidepressants. Another review tried to answer the question about antidepressants (in unipolar disorder), but only had to conclude that both groups of drugs are effective, but there were too few qualitative comparisons.
Lithium may help against schizoaffective disorders , but the evidence is 22 clinical trials with a high risk of biased interpretation, so it is not worth jumping to conclusions.
The lists (not) included
And now about lithium ascorbate . There is no drug Normotim in the state register of approved clinical trials . What’s the matter? And the fact that this is not a medicine, but a dietary supplement. Moreover, it was registered recently, because the database of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare, which has not been updated for a year, can not be found either .
A double-blind, randomized, placebo-controlled method is a method of clinical trial of drugs in which subjects are not privy to important details of the study being conducted. “Double-blind” means that neither the subjects nor the experimenters know about who is being treated with what, “randomized” means that the distribution of groups is random, and the placebo is used to show that the effect of the drug is not based on self-hypnosis and that this medicine works better than a tablet without an active ingredient. This method prevents subjective bias in the results. Sometimes the control group is given another drug with already proven efficacy, rather than a placebo, to show that the drug not only cures better than nothing, but also outperforms analogues.
One tablet of Normotim will contain 6.36 mg of lithium ascorbate . Analog tablets – a popular drug with lithium carbonate – contain 300 mg of active ingredient, which is almost 47 times more. Even if we begin to recalculate the content of lithium separately, without the carbonate or ascorbate part, this ratio does not change in favor of Normotim : lithium alone in a dose of Sedalite will be about 56 mg. Not surprisingly, at the very bottom of the site, we will see a warning: “not a drug.” And if he is not, then what is the demand from him?
Despite this, the authors of the study on the Normotim website claim that the supplement creates therapeutic concentrations of lithium in the blood (they explain this by the increased bioavailability of ascorbate compared to carbonate and other compounds). True, in this study there is absolutely no control group, there are many diagnoses (and the condition with them, as we found out above, can itself change cyclically), and there are only 54 patients. In addition, the authors declare that toxicity tests were carried out in rodents, and in another Normotim’s work was also credited with combating obesity and depression (defined as “unstable emotional background”).
About tdayte prefer drug rather than supplements
Do not forget that a single dose for a patient can reach a couple of grams of active ingredient. Yes, they do not prescribe it immediately, but select it, focusing on the required concentration of lithium, which is judged by blood tests. Normotim tablets for the required dosage would have to be swallowed in hundreds. The manufacturer’s statement of therapeutic blood values was only published in a study on the drug’s website. On the one hand, it has not been proven, but even if it is true, it only suggests that Normotim is dangerous, because it will be difficult to calculate a harmless dose. In order for the lithium preparation not to harm, the effect of a particular salt must be investigated. This was not done for the ascorbate .
“This is at best a harmless vitamin , and no one has tested the safety of people with electrolyte metabolism and endocrine disorders. Lithium is not a harmless substance after all. But the main thing is that this Skolkovo development is not a cure for BAR, ” writes Maria Gantman , a psychiatrist and a former research fellow at the Scientific Center for Mental Health of the Russian Academy of Medical Sciences.
In Normotim there are also vitamins, but mental disorders are not vitamin deficiency. Treat the drug exactly like a dietary supplement. Therefore, if you are going to really be treated, then Normotim will not help with this. It is better to turn to real drugs, for example, based on lithium carbonate, and with an adequate dosage. Yes, they will have to be used under the supervision of doctors and with measurements of their concentration in the blood. But they work and are even included in international recommendations.