It should be mentioned, that the majority of clinical studies cited here are the most questionable and poorly documented as standardized psychological measures were not used in the earlier studies. Indeed, some of them did not use randomization, or blinding of subjects. However, the main problem in assessment of these studies is that the Soviet diagnostic criteria were different from commonly used criteria in the rest of the world [ 169 171 ]. The diagnostic criteria used in the USSR prior to 1990 for schizophrenia was particularly idiosyncratic, overused, and misapplied to other conditions [ 169 171 ]. For example, some patients who would be diagnosed as having psychotic depression, schizotypal disorder, schizoaffective disorder, or bipolar disorder by a non-Soviet psychiatrist would have been diagnosed as schizophrenic by a Soviet psychiatrists [ 166 168 ]. Indeed, the term “sluggish-schizophrenia” was particularly misused [ 172 ]. The diagnoses of asthenia and neuroasthenia include a very heterogeneous group of patients with mixed psychological and physical disorders, making the studies more difficult to interpret.

Nevertheless, in spite of numerous shortcomings, which reduced the quality of evidences obtained in the early clinical studies in Russia, these scientific evidences provide important information about efficacy and safety of adaptogens in the treatment of psychiatric disorders, table 6 . Some of these publications are discussed below.

4.2.1. Rhodiola Rosea

Rhodiola rosea extract in patients suffering from illnesses, such as asthenia syndrome, neuroses, vascular dystonia, hypotension, and schizophrenia (remissions of asthenic type). The advised dosage of the extract was 5–25 drops (in a quarter of a glass of water) three times daily and should be taken 15–30 minutes before meals. Although, the duration of the therapy was individually determined and varied from 10 days to 4 months [ In 1969, the Pharmacological Committee of the Ministry of Health of the USSR recommended the medicinal use ofextract in patients suffering from illnesses, such as asthenia syndrome, neuroses, vascular dystonia, hypotension, and schizophrenia (remissions of asthenic type). The advised dosage of the extract was 5–25 drops (in a quarter of a glass of water) three times daily and should be taken 15–30 minutes before meals. Although, the duration of the therapy was individually determined and varied from 10 days to 4 months [ 173 174 ].

Rhodiola rosea extract was reported to be a valuable medicine in essentially healthy people placed under heavy physical or mental workloads [ Rhodiola rosea extract it has been advised that doses should be taken in the morning, or in the morning and the afternoon, for at least a few days prior to a period of intensive mental work for a during 2–3 weeks. In cases of hard mental work, it has been recommended that duration of Rhodiola rosea therapy last for the duration of the period. It has been reported that therapy with Rhodiola rosea extract prevented exhaustion and fatigue during work requiring long intensive mental activity [ The symptomatic characteristics of asthenic syndrome is general weakness, reduced working capacity, low memory, irritability, headaches, insomnia, and poor appetite. These symptoms are frequently observed after intensive work, which requires high levels of mental exertion. Indeed, theextract was reported to be a valuable medicine in essentially healthy people placed under heavy physical or mental workloads [ 175 176 ]. Furthermore, to take advantage of the prophylactic measures ofextract it has been advised that doses should be taken in the morning, or in the morning and the afternoon, for at least a few days prior to a period of intensive mental work for a during 2–3 weeks. In cases of hard mental work, it has been recommended that duration oftherapy last for the duration of the period. It has been reported that therapy withextract prevented exhaustion and fatigue during work requiring long intensive mental activity [ 175 176 ].

Rhodiola rosea extract was also observed in an open label, uncontrolled study in 128 patients with pronounced states of fatigue of different genesis [ R. rosea extract and as a result the clinical symptoms of fatigue were considerably improved or disappeared completely. Their diagnosis of fatigue was confirmed by psychological examinations and increased mental work capacity. Indeed, there are also therapeutic effects of Rhodiola rosea extract in exhaustion due to psychogenic and somatogenic origin (82%) or in patients convalescing from somatic and infectious diseases (80%) [ Rhodiola rosea extract. Thus, these patients improved in focusing their attention, and headaches vanished. Furthermore, Rhodiola rosea extract reduced and eliminated general weakness and fatigue in cases of traumatic cerebrastenia injury and also significantly facilitated the normalisation of the autonomic functions in this group of patients [ The positive therapeutic effect ofextract was also observed in an open label, uncontrolled study in 128 patients with pronounced states of fatigue of different genesis [ 175 ]. For example, 128 patients between 17 and 55 years of age (male/female: 75/53) were treated with anextract and as a result the clinical symptoms of fatigue were considerably improved or disappeared completely. Their diagnosis of fatigue was confirmed by psychological examinations and increased mental work capacity. Indeed, there are also therapeutic effects ofextract in exhaustion due to psychogenic and somatogenic origin (82%) or in patients convalescing from somatic and infectious diseases (80%) [ 175 ]. For example, patients suffering from post-influenza fatigue showed improved mental and physical working capacity already on the third day after intake ofextract. Thus, these patients improved in focusing their attention, and headaches vanished. Furthermore,extract reduced and eliminated general weakness and fatigue in cases of traumatic cerebrastenia injury and also significantly facilitated the normalisation of the autonomic functions in this group of patients [ 175 ].

Rhodiola rosea extract has a pronounced therapeutic effect on neuroses (exhaustings depression) was reported in an open label study on 65 poorly characterized mixed patient population [ Rhodiola rosea extract (10 drops; 3 times daily for 10 days) the excitation and inhibitory processes intensified and mobility normalized. In fact, the conditional motor reflexes also changed. It was seen that their value and stability increased and that the latent period reduced, whilst concentration improved and the interaction of both signal systems were normalized. Furthermore, the extract therapy reduced the latent time of verbal reactions and improved attention and memory. Thatextract has a pronounced therapeutic effect on neuroses (exhaustings depression) was reported in an open label study on 65 poorly characterized mixed patient population [ 177 ] suffering from insomnia, high irritability and various somatic disorders. The state of the higher nervous activity was tested in these patients with the help of a verbal test and the conditional motor reflexes were tested with verbal reinforcement, in conjunction with routine clinical examinations. The results of the verbal tests showed that the latent period of verbal reactions in most of the subjects was long-up to 1.8–6.0 s (a normal period is 1.5 s). Indeed, results of the motor-verbal test prior to treatment showed that two thirds of the patients performed poorly in mental work situations. However, after a course of therapy withextract (10 drops; 3 times daily for 10 days) the excitation and inhibitory processes intensified and mobility normalized. In fact, the conditional motor reflexes also changed. It was seen that their value and stability increased and that the latent period reduced, whilst concentration improved and the interaction of both signal systems were normalized. Furthermore, the extract therapy reduced the latent time of verbal reactions and improved attention and memory.

Indeed, the authors observed a clinical improvement, such as disappearance of irritability and unpleasant sensations in the heart region and improvement of sleep and appetite, in these patients. Similar clinical results were obtained in another study with 177 patients suffering from vascular hypotension. The authors observed that a course of therapy with Rhodiola rosea extract stabilized, completed or partially normalized 92% of the hypotensive patients. Thus, the patients felt better, headaches disappeared, sleep became normal and they recovered their working capacity.

Rhodiola rosea extract was able to diminish or eliminate depressive symptoms. For example, Mikhailova reported that an open label clinical trial of Rhodiola extract (15 drops three times daily for a month or up to four months in some cases) in 58 patients with stress induced depression (asthenia of exogenous organic genesis), showed a remarkable symptomatic improvenment was observed [ i.e., difficulties in falling asleep, waking up during the night) noted sleep improvements. However, it should be noted that sleep normalisation and reduction of other asthenic symptoms depended on the intensity of these disorders [ Several clinical studies of the dynamics of asthenic symptoms have showed thatextract was able to diminish or eliminate depressive symptoms. For example, Mikhailova reported that an open label clinical trial ofextract (15 drops three times daily for a month or up to four months in some cases) in 58 patients with stress induced depression (asthenia of exogenous organic genesis), showed a remarkable symptomatic improvenment was observed [ 178 ]. Their general weakness or feeling of being worn out in the morning with a high fatigability, and hypersomnia during the day (without disturbance of the following night’s sleep) either disappeared or became considerably reduced. In addition, no side effects were observed except in one patient who showed sleep disturbance. In this case, the dose was reduced to 6 drops twice a day and the adverse symptoms immediately disappeared. Indeed, most patients (39/58) suffering from pre-and intra somnia (difficulties in falling asleep, waking up during the night) noted sleep improvements. However, it should be noted that sleep normalisation and reduction of other asthenic symptoms depended on the intensity of these disorders [ 178 ].

Rhodiola rosea [ R. rosea increased general activity, intellectual and physical productivity of patients, and decreases side effects induced by the tricyclic anti-depressants. Furthermore, it was seen that patients in depressive states of different genesis normally treated with tricyclic anti-depressants reduced the time spent in hospital whilst using them in combination with 179 ]. The authors observed adjuvant therapy withincreased general activity, intellectual and physical productivity of patients, and decreases side effects induced by the tricyclic anti-depressants.

Rhodiola rosea extract was successfully used in the alleviation of side effects after psychotropic therapy in schizophrenic patients [ Rhodiola rosea extract (25–40 drops; 2–3 times daily) for a duration of 1–1.5 months. In addition, 19 of these patients received a combination of a high dose of Rhodiola rosea extract and cholinolytic Romparkin (Trihexylphenidyl), as this preparation alone failed to eliminate or soothe the clinical symptoms of the side effects in this group of patients. The results of this study showed that Rhodiola rosea extract had the most pronounced therapeutic effect on symptoms of Parkinsonism and asthenia. In was reported thatextract was successfully used in the alleviation of side effects after psychotropic therapy in schizophrenic patients [ 176 ]. In this short communication is mentioned that 31 patients suffering from pronounced clinical symptoms of extrapyramidal syndrome, which resulted from therapy by neuroleptics, received a high dose ofextract (25–40 drops; 2–3 times daily) for a duration of 1–1.5 months. In addition, 19 of these patients received a combination of a high dose ofextract and cholinolytic Romparkin (Trihexylphenidyl), as this preparation alone failed to eliminate or soothe the clinical symptoms of the side effects in this group of patients. The results of this study showed thatextract had the most pronounced therapeutic effect on symptoms of Parkinsonism and asthenia.

Rhodiola rosea extract in the USSR was based on the following findings: (i) as stimulants for essentially healthy people in a state of fatigue and for patients with asthenic states during the rehabilitation period following somatic or infectious diseases. (ii) for essentially healthy people Rhodiola rosea extract should be taken several days before the expected strain and during the whole period of increased mental exertion as a prophylaxis. (iii) to recover mental and physical working capacity during and after long periods of intensive mental and physical work. (iv) and sexual disorders related to impotence in males. (v) in psychiatric practice as an adjuvant to counteract side effects of psychopharmacological therapy [ 28 ]. In conclusion, the introduction ofextract in the USSR was based on the following findings: