Benzodiazepines

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Benzodiazepines (colloquial short form Benzos ) are polycyclic organic compounds based on a bicyclic body in which a benzene - is connected to a diazepine ring . Benzodiazepines have an anxiolytic (anxiety-relieving), sedative (calming), muscle-relaxing (muscle-relaxing) and hypnotic (sleep-promoting to sleep-inducing) effect. Some benzodiazepines also have anticonvulsant (anticonvulsant) properties and are therefore used as anti-epileptic drugs . In animal experiments, they have an analgesic effect (pain reliever). Because of their central nervous effects, this group of substances is one of the psychoactive substances ; some of their representatives are therefore used in medicine as psychotropic drugs. The benzodiazepines diazepam , lorazepam, and midazolam are listed on the World Health Organization's Essential Medicines List. Compared to barbiturates , which have a similar application profile, benzodiazepines have the advantage of a greater distance between the therapeutic and toxic dose and have therefore largely replaced them in medical practice since their market launch.

All benzodiazepines bind to GABA receptors , the most important inhibitory receptors in the central nervous system . Benzodiazepines have not least because of their action on the GABA-budget (similar to ethanol and barbiturates), and because of their high effectiveness and usually rapid onset of action (depending on application) a high potential for dependency . Rapid tolerance development is also not uncommon, which is why long-term therapy is usually avoided.

history

Even before the benzodiazepines, there were effective sleeping pills and sedatives such as bromine , sulfonal and barbiturates ; however, they were associated with more severe side effects and risks. From the group of benzodiazepines, chlordiazepoxide was the first compound on the market. It was developed by Leo Sternbach for the pharmaceutical company Hoffmann-La Roche and marketed in 1960 under the trade name Librium . Based on their pharmacodynamic effects, benzodiazepines were classified as potent anticonvulsants in the 1960s .

In the further course of research mainly compounds with a lactam structure were introduced (R 2 = O ). So also the diazepam developed by Leo Sternbach . It was brought to market in 1963 by Hoffmann-La Roche under the trade name Valium . As early as 1977, diazepam was included in the list of essential drugs of the World Health Organization . In Germany, diazepam was still the most frequently prescribed benzodiazepine in 2005.

Chemistry and structure

Benzodiazepine Structural Formula V1.svg
Benzodiazepine scaffold
Structural differences of benzodiazepines
R 1 R 2 R 7 R 2 ' Surname
H O NO 2 Cl Clonazepam
H O Cl Cl Delorazepam
CH 3 O Cl H Diazepam
CH 3 O NO 2 F. Flunitrazepam
H O Br Cl Phenazepam
C 2 H 4 N (C 2 H 5 ) 2 O Cl F. Flurazepam
CH 3 H Cl H Medazepam
H O NO 2 H Nitrazepam
C 4 H 7 O Cl H Prazepam
CH 3 O Cl Cl Diclazepam
H O Cl H North Azepam

All benzodiazepines contain a system of two interconnected ring-shaped structures: the benzene and diazepine rings are condensed to form a bicyclic ring system. Its larger seven-membered unsaturated ring contains two nitrogen atoms and thus belongs to the heterocyclic compounds . According to the Hantzsch-Widman nomenclature for heterocyclic systems, such a ring is referred to as a diazepine. In the case of the benzodiazepines, a benzene ring is fused to the diazepine ring .

Thienodiazepine scaffold

As drugs are primarily benzo-1,4-diazepines used (see above structural formula, in the 2'-position of the addition at the 5-position of a further six-membered ring such as benzene phenyl group may be a halogen as a substituent ), cyclohexene or pyridine wear . In clobazam , the only representative of the benzo-1,5-diazepines used, this third ring is bound to its N atom in the 5-position.

The thienodiazepines are structured similarly to the benzodiazepines as heterocycles that contain a diazepine ring; however, a thiophene ring instead of a benzene ring is fused to these in their case .

Z-Drugs have certain structural similarities, but do not have a benzodiazepine base. However, they show a pharmacological action profile similar to the benzodiazepines, since they bind to the same receptors.

pharmacology

Mechanism of action

Schematic representation of the GABA A receptor in plan view. The five subunits - in this example consisting of α 1 β 2 γ 2 - are evenly arranged around an axis and have a pore, the channel lumen , in their center . The binding site for benzodiazepines is located between the alpha and gamma subunits.

Benzodiazepines act as allosteric modulators at the GABA A receptor , they complex with the benzodiazepine (BzD) binding site of this ionotropic receptor. This connection changes the shape of the receptor and thus modulates the activation of the receptor. The positive modulation caused by classic benzodiazepines increases the affinity of the inhibitory neurotransmitter GABA at its orthosteric binding site. This increases the likelihood of the chloride channel opening and the influx of chloride ions into the nerve cell is increased, which in turn leads to a lower excitability of the neuron membrane (due to hyperpolarization and short-circuiting of EPSPs ).

Classic benzodiazepines bind to GABA A receptors with the alpha subunits α 1 , α 2 , α 3 and α 5 ; they have no affinity for α 4 and α 6 .

Benzodiazepines have different effects from barbiturates . The following mechanisms are responsible for this:

  • Benzodiazepines only work together with GABA and on their own are not able to open the GABA A receptor. They are correctly referred to as positive, negative or, in rare cases, silent / neutral allosteric modulators. The terms agonist , antagonist and inverse agonist do appear in the literature to designate these active ingredients, but they can be misunderstood and should be avoided with pure modulators.
  • Benzodiazepines work more strongly on synapses that are low in GABA than on those that are high in GABA.
  • Weak transmitter responses are amplified more than strong transmitter responses. One speaks of an activity-dependent effect (use dependence). This effect could also be responsible for a relatively specific effect of the benzodiazepines (anxiolytic, anticonvulsant, central muscle relaxing, sedative / hypnotic, amnestic see below), despite the ubiquitous distribution of the GABA receptors in the brain and spinal cord.

Even high doses of benzodiazepines do not increase the maximum effect (which theoretically could also be achieved with GABA alone). You just lower the dose of GABA, which leads to a maximum effect. In pharmacological terms, they lead to a left shift in the dose-response curve .

Effects

Benzodiazepines work

In animal experiments, the benzodiazepine diazepam has an analgesic (analgesic) effect when injected into the spinal cord , particularly in the case of neuropathic pain . It is believed that the effects on the GABA receptor are responsible for this effect.

Benzodiazepines found in psychiatry use in the treatment of anxiety - and restlessness, as rescue medication for epileptic seizures and as a falling asleep and sleeping pills . They are also prescribed as premedication before operations so that the patient is as relaxed and free of fear as possible. Benzodiazepines are also used to induce anesthesia and to supplement operations performed with other narcotics , among other things because of their relatively low effects on the cardiovascular system .

While in animal experiments a withdrawal syndrome can be triggered after one week of continuous administration of the maximum dose , this is only possible in humans in therapeutic doses after at least 8 weeks of exposure. As a rule, it is recommended not to exceed 4 weeks in order to minimize the risk of developing addiction . In summary, the indication for the prescription of benzodiazepines must be viewed critically and the application as short as possible and the dose as low as possible. In the case of long-term treatment, the dangers must be carefully weighed against the therapeutic benefit. Most benzodiazepines are generally not approved for long-term treatment. Exceptions are the antiepileptic benzodiazepines, which, if indicated, often have to be taken for life.

Benzodiazepine preparations are dose-dependent and, depending on the substance, have different degrees of respiratory depression , i.e. i.e., they dampen the respiratory center . Life- threatening intoxications are rare when BZD is taken alone, but the risk increases with simultaneous consumption of alcohol or the simultaneous administration of other CNS-effective preparations, especially the opioids , as these themselves have a strong respiratory depressive effect. In addition, when opioids and benzodiazepines are taken at the same time, their sedative effects are mutually enhanced. There is also a so-called cross - tolerance between benzodiazepines and alcohol . Benzodiazepines affect the reaction time. The driver is unable to drive for at least the first few days of taking benzodiazepine-containing drugs . In the course of continued therapy, the attending physician decides on a case-by-case basis whether driving a motor vehicle or operating dangerous machines is possible again.

Benzodiazepines are considered to be the drugs with the highest rate of abuse worldwide.

There is clear evidence of risks to the human fetus associated with benzodiazepine administration during pregnancy. In animal experiments, there was also evidence of behavioral disorders in the offspring when the dams were given benzodiazepines during pregnancy.

Contraindications

Contraindications to the use of benzodiazepines:

Antidote

Flumazenil , a reversible competitive antagonist , temporarily reverses the effect of benzodiazepines after intravenous administration (half-life approx. 45 min). In the course of treatment of an acute overdose, it is essential to pay attention to the possible need to continue administering further doses of flumazenil, since the half-life of about 45 minutes is much shorter than that of most benzodiazepines (half-life about 60 min to 120 h).

Individual substances

With a few exceptions such as chlorazepate , the names of benzodiazepine active ingredients often end with -azepam or -zolam . The following table provides an overview of the pharmacological data of the benzodiazepines and marketing information.

Active ingredient Trade name (s) Effect type Chemical name Plasma half-life
(metabolite half-life )
Equivalent dose to 10 mg diazepam Year of
launch
Adinazolam Deracyn (FR) Tranquilizer, anxiolytic 8-Chloro-1- (dimethylaminomethyl) -6-phenyl-4 H - [1,2,4] triazolo [4,3- a ] [1,4] benzodiazepine 1.5-3 h 1976
Alprazolam Tafil (D),
Xanax (CH, USA),
Xanax retard (CH, USA),
Xanor (A),
various generics (D, A)
Tranquilizer, anxiolytic 8-Chloro-1-methyl-6-phenyl-4 H - [1,2,4] -triazolo [4,3- a ] [1,4] benzodiazepine 12-15 h 1.5 mg 1984
Bromazepam Bromazanil (D),
Gityl (D),
Lexostad (D),
Lexotanil (D, A, CH),
Bromazepam OPT (D),
Normoc (D),
various generics (D, A)
Tranquilizer, anxiolytic 7-bromo-2,3-dihydro-5- (2-pyridyl) - 1 H -1,4-benzodiazepin-2-one 15-28 h 6 mg 1977
Camazepam Albego (CH, ES, IT) Anxiolytic, hypnotic 7-chloro-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl N, N-dimethylcarbamate 6-11 h 10-20 mg 1978
Chlordiazepoxide Librax (CH),
Librocol (CH),
Limbitrol (A, CH)
Tranquilizers 7-chloro-2-methylamino-5-phenyl-3 H -1,4-benzodiazepine-4-oxide 5–30 h (48–96 h) 20 mg 1960
Cinolazepam Gerodorm (BG, CZ, HU, SK, RO) Hypnotic 7-chloro-5- (2-fluorophenyl) -2,3-dihydro-3-hydroxy-2-oxo-1 H -1,4-benzodiazepin-1-propionitrile 4-6 h 40 mg 1992
Clobazam Frisium (D, A),
Urbadan (NL),
Urbanyl (CH),
Noiafren (ES),
Castilium (PT)
Tranquilizer, anxiolytic, anti-epileptic 7-chloro-1-methyl-5-phenyl-1 H -1,5 -benzodiazepine-2,4 (3 H , 5 H ) -dione 18 h (36–80–120 h) 20 mg 1977
Clonazepam Rivotril (D, CH),
Antelepsin (D)
Anti-epileptic 5- (2-chlorophenyl) -2,3-dihydro-7-nitro-1 H -1,4-benzodiazepin-2-one 30-40 h 2 mg 1976
Clonazolam Anti-epileptic 6- (2-Chlorophenyl) -1-methyl-8-nitro-4 H - s -triazolo [4,3- a ] -1,4-benzodiazepine 16 h 0.5 mg
Clorazepate Tranxene (international trade name),
Tranxilium (D, A, CH)
Tranquilizers 7-chloro-2,3-dihydro-2,2-dihydroxy-5-phenyl-1 H -1,4-benzodiazepine-3-carboxylic acid 2 h [approx. 30–90 h for the active metabolite nordazepam ( N- desmethyldiazepam)] 20 mg 1969
Cloxazolam Olcadil (DE, CH, AT),
Akton (BE, LU),
Cloxam (PT),
Elum (BE),
Lubalix (CH),
Sepazon (HK, JP)
Tranquilizers 10-Chloro-11b- (2-chlorophenyl) -2,3,7,11b-tetrahydro [1,3] oxazolo [3,2- d ] [1,4] benzodiazepin-6-one (55-75 h) 4 mg
Delorazepam Dadumir (IT),
EN (IT),
various generics (IT)
Anxiolytic, premedication 7-chloro-5- (2-chlorophenyl) -1,3-dihydro-1,4-benzodiazepin-2 (2 H ) -one 80-115 h 1 mg 1977
Diazepam Diazep-CT (D),
Faustan (D),
Gewacalm (A),
Paceum (CH),
Psychopax (A, CH),
Stesolid (D, A, CH),
Valiquid (D),
Valium (D, A, CH , L),
Valocordin-Diazepam (D),
various generics (D, CH)
Tranquilizer, anti-epileptic, anxiolytic 7-chloro-2,3-dihydro-1-methyl-5-phenyl-1 H -1,4-benzodiazepin-2-one 24–48 h [approx. 30–90 h for the active metabolite nordazepam (N-desmethyldiazepam)] 10 mg 1963
Diclazepam Tranquilizer, anxiolytic, muscle relaxant 7-chloro-1-methyl-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one 42 h 1 mg
Doxefazepam Doxans (IT) Hypnotic 7-chloro-5- (2-fluorophenyl) -3-hydroxy-1- (2-hydroxyethyl) -2,3-dihydro-1 H -1,4-benzodiazepin-2-one 3-4 h 1984
Estazolam Domnamid (DK),
Eszo (TW),
Esilgan (IT)
Eurodin (JP),
Nuctalon (FR),
ProSom (USA),

Sedarest (PE)

Hypnotic 8-Chloro-6-phenyl-4 H - s -triazolo- [4,3a] [1,4] benzodiazepine 10–24 h 1-2 mg 1975
Flualprazolam 6- (2-Fluorophenyl) -1-methyl-8-chloro-4H- [1,2,4] triazolo [4,3-a] [1,4] benzodiazepine 20 h 0.25 mg
Flubromazepam Hypnotic, anxiolytic, tranquilizer, muscle relaxant, anti-epileptic 7-Bromo-5- (2-fluorophenyl) -1,3-dihydro-1,4-benzodiazepin-2-one 106 h 4 mg
Flubromazolam 8-Bromo-6- (2-fluorophenyl) -1-methyl-4 H - [1,2,4] triazolo [4,3- a ] [1,4] benzodiazepine 20 h 0.25 mg
Fludiazepam Erispan (JP, TW) Tranquilizer, hypnotic 7-chloro-5- (2-fluorophenyl) -1-methyl-1,3-dihydro-2 H -1,4-benzodiazepin-2-one 10-30 h 1 mg
Flunitrazepam Fluninoc (D),
Rohypnol (D, A, CH),
some generics (D)
Hypnotic 5- (2-fluorophenyl) -2,3-dihydro-1-methyl-7-nitro-1 H -1,4-benzodiazepin-2-one 16-35 h 0.5-1 mg 1975
Flunitrazolam 6- (2-Fluorophenyl) -1-methyl-8-nitro-4 H -benzo [ f ] [1,2,4] triazolo [4,3- a ] [1,4] diazepine 0.5 mg
Flurazepam Dalmadorm (D, CH),
Staurodorm (D),
Flurazepam Real (D)
Hypnotic 7-chloro-1- (2-diethylaminoethyl) -5- (2-fluorophenyl) -2,3-dihydro-1 H -1,4-benzodiazepin-2-one 1.5 h [approx. 30–90 h for the active metabolite nordazepam (N-desmethyldiazepam)] 15-30 mg 1974
Flutazolam Coreminal (JP) Tranquilizers 10-chloro-11 b - (2-fluorophenyl) -7- (2-hydroxyethyl) -3,5-dihydro-2 H - [1,3] oxazolo [3,2-d] [1,4] benzodiazepine- 6-one 3-4 h 30 mg
Flutoprazepam Restas (JP) Tranquilizers 7-chloro-1- (cyclopropylmethyl) -5- (2-fluorophenyl) -3 H -1,4-benzodiazepin-2-one (60–90 h) 3-4 mg
Halazepam Alapryl (ES),
Pacinone (BE, NL),
Paxipam (IT, USA)
Tranquilizers 7-chloro-2,3-dihydro-5-phenyl-1- (2,2,2-trifluoroethyl) -1 H -1,4-benzodiazepin-2-one (30-100 h) 20 mg 1981
Loprazolam Sonin (D) Tranquilizers 6- (2-Chlorophenyl) -2,4-dihydro-2 - [(4-methyl-1-piperazinyl) methylene] -8-nitro-1 H -imidazo [1,2- a ] [1,4] benzodiazepine -1-on 8-9 h 1-1.5 mg 1987
Lorazepam Ativan (USA, GB),
Lorazepam dura (D),
Merlit (A),
Tavor (D),
Temesta (CH, A, L, B),
Tolid (D),
various generics
Tranquilizer, hypnotic, anti-epileptic ( RS ) -7-chloro-5- (2-chlorophenyl) -2,3-dihydro-3-hydroxy-1 H -1,4-benzodiazepin-2-one 12.9-16.2 hours 2 mg 1963
Lormetazepam Ergocalm (D),
Loramet (CH),
Loretam (D),
Noctamid (A, D, CH),
Sedalam (D),
various generics (D)
Hypnotic ( RS ) -7-Chloro-5- (2-chlorophenyl) -2,3-dihydro-3-hydroxy-1-methyl-1 H -1,4-benzodiazepin-2-one 10-14 h 1 mg 1980
Ketazolam Unakalm,
Ansieten,
Anxon,
Loftran,
Anseren
Tranquilizer, anti-epileptic, anxiolytic 11-chloro-8,12b-dihydro-2,8-dimethyl-12b-phenyl-4 H - [1,3] oxazino [3,2- d ] [1,4] benzodiazepine-4,7 (6 H ) -dion 50 h (36–200 h, Northazepam ) 15-20 mg
Meclonazepam (3 S ) -5- (2-Chlorophenyl) -3-methyl-7-nitro-1,3-dihydro-2 H -1,4-benzodiazepin-2-one 1 mg
Medazepam Rudotel (D),
Nobrium (D)
Tranquilizers 7-chloro-2,3-dihydro-1-methyl-5-phenyl-1 H -1,4-benzodiazepine 2–5 h [approx. 30–90 h for the active metabolite nordazepam (N-desmethyldiazepam)] 20 mg 1968
Metaclazepam Talis (DE, AT) Anxiolytic 7-Bromo-5- (2-chlorophenyl) -2-methoxymethyl-1-methyl-2,3-dihydro-1 H -1,4-benzodiazepine 16 h 10 mg 1988
Mexazolam Melex (JP),
Sedoxil (PT)
Anxiolytic 10-Chloro-11b- (2-chlorophenyl) -3-methyl-2,3,7,11b-tetrahydrooxazolo [3,2- d ] [1,4] benzodiazepin-6-one (74 h) 10 mg
Midazolam Buccolam (D, CH),
Dormicum (D, CH),
various generics (CH)
Short hypnotic 8-chloro-6- (2-fluorophenyl) -1-methyl-4 H -imidazo [1,5- a ] [1,4] benzodiazepine 1.5-2.5 h 7.5 mg orally (1 mg i.v.) 1985
Nifoxipam 5- (2-fluorophenyl) -3-hydroxy-7-nitro-1,3-dihydro-2 H -1,4-benzodiazepin-2-one
Nimetazepam Erimin (JP) Hypnotic 2,3-Dihydro-7-nitro-5-phenyl-1-methyl-1 H -1,4-benzodiazepin-2-one 18-30 h 5 mg
Nitrazepam Dormo-Puren (D),
Imeson (D),
Mogadan (D),
Mogadon (A, CH),
Novanox (D),
Radedorm (D)
Hypnotic, anti-epileptic 2,3-Dihydro-7-nitro-5-phenyl-1 H -1,4-benzodiazepin-2-one 18-30 h 5 mg 1965
North Azepam Tranquilizers 7-chloro-2,3-dihydro-5-phenyl-1 H -1,4-benzodiazepin-2-one 50–90 h (8 h) 20 mg
Oxazepam Adumbran (D, A),
Anxiolit (A, CH),
Durazepam (D),
Praxiten (D, A),
Seresta (CH),
various generics (D)
Tranquilizers ( RS ) -7-chloro-2,3-dihydro-3-hydroxy-5-phenyl-1 H -1,4-benzodiazepin-2-one 5-15 h 30 mg 1965
Oxazolam Sera (TH),
Serebon (HK),
Serenal (JP)
Tranquilizers (2 RS , 11b SR ) -10-Chloro-2-methyl-11b-phenyl-2,3,7,11b-tetrahydro [1,3] oxazolo [3,2-d] [1,4] benzodiazepine-6 (5 H ) -one 1.5 h [approx. 30–90 h for the active metabolite nordazepam ( N- desmethyldiazepam)] 40 mg
Phenazepam Phenazepam (RU),
Fenazepam (GE),
Fenazepams (LT),
Phenzepine (GE)
Tranquilizers 7-Bromo-5- (2-chlorophenyl) -1,3-dihydro-1,4-benzodiazepin-2-one (60 h) 1 mg
Pinazepam Domar (IT),
Duna (ES, IT)
Anxiolytic 7-chloro-5-phenyl-1- (prop-2-in-1-yl) -1,3-dihydro-2 H -1,4-benzodiazepin-2-one 10-15 h [approx. 30–90 h for the active metabolite nordazepam ( N- desmethyldiazepam)] 20 mg 1975
Prazepam Demetrin (CH) Tranquilizers 7-chloro-1- (cyclopropylmethyl) -2,3-dihydro-5-phenyl-1 H -1,4-benzodiazepin-2-one 1.5 h [approx. 30–90 h for the active metabolite nordazepam (N-desmethyldiazepam)] 20 mg 1973
Pyrazolam Anxiolytic 8-Bromo-1-methyl-6- (pyridin-2-yl) -4 H - [1,2,4] triazolo [4,3- a ] [1,4] benzodiazepine 16-18 h 1 mg
Quazepam Doral (US, JP),
Quiedorm (ES)
Hypnotic 7-chloro-5- (2-fluorophenyl) -2,3-dihydro-1- (2,2,2-trifluoroethyl) -1 H -1,4-benzodiazepine-2-thione (25–41 h) 20 mg 1985
Temazepam Normison (CH),
Planum (D),
Remestan (D),
Temazep (D),
various generics
Hypnotic ( RS ) -7-chloro-3-hydroxy-1-methyl-5-phenyl-1 H -1,4-benzodiazepin-2 (3 H ) -one 5-13 h 20 mg 1969
Tetrazepam Musaril (D),
Myolastan (A),
Rilex (D),
various generics (D, A)
Myotonolytic (muscle relaxant) 7-chloro-5- (1-cyclohexenyl) -1-methyl-1 H -1,4-benzodiazepin-2 (3 H ) -one 18 h 20 mg 1981
Triazolam Halcion (D, A, CH) Hypnotic 8-chloro-6- (2-chlorophenyl) -1-methyl-4 H -1,2,4-triazolo [4,3- a ] [1,4] benzodiazepine 1.4-4.6 h 0.5 mg 1982

A non-psychoactive benzodiazepine is netazepid , which is being developed to treat cancer. Tifluadom is no longer used due to adverse drug effects .

Analytics

Due to the toxicological properties of the benzodiazepines, there is great interest in the legally secure qualitative and quantitative determination in the most varied of objects to be examined. The coupling between gas chromatography , HPLC and mass spectrometry are generally used as analytical methods after adequate sample preparation . For the detection of naturally occurring benzodiazepines in biological materials, such as. B. food, plants, human brain tissue samples from before 1960 u. a., an extensive investigation using GC / MS coupling and radioreceptor assays is available.

Prescription Practice in Germany and Criticism

The prescription of benzodiazepines in Germany decreased from 228 million defined daily therapy doses (DDD) in 1995 to 68 million DDD in 2004.

However, the number of prescriptions on private prescriptions has increased, according to the German Society for Psychiatry, Psychotherapy and Neurology (DGPPN):

“The prescription of benzodiazepines at the expense of the statutory health insurances (GKV) fell from 11 million (1993) to 2.5 million packs (2004), while according to purchasing statistics the dispensing by pharmacies only from 12.7 million to 5.6 Million packs decreased. Z-Drugs (zaleplon, zopiclone, zolpidem) increased in the GKV from 2.1 million (1993) to 3.8 million packs (2004), the dispensing by pharmacies, however, according to purchasing statistics, was much more pronounced of 2.2 million. to 7.4 million packages. The authors Hoffmann, Glaeske, Scharffetter interpret this correctly as an increased prescription on a private prescription. The database does not allow the insurance status (GKV / PKV) of the patient to be determined. However, it seems plausible to assume that the increasing number of prescriptions of benzodiazepine hypnotics on private prescription also apply to persons insured with statutory health insurance. Ultimately, the recommendations of the AkdÄ are based on the assumption that the prescription of benzodiazepine hypnotics on a private prescription by statutory health insurance patients indicates an abuse of this group of substances, which should be made less transparent and understandable through such a prescription. "

- German Society for Psychiatry, Psychotherapy and Neurology (DGPPN), opinion on the “Recommendations of the Drugs Commission of the German Medical Association on the Prescription of Benzodiazepine-Containing Hypnotics” of September 11, 2008

Due to the high potential for addiction (which was almost entirely unknown at the time when the first benzodiazepines were launched), but also critical (specialist) press reports, especially on empirical studies that showed a possibly increased risk of dementia, the prescriptions of benzodiazepine-containing drugs in Germany are in the in the last few years until 2018. This is particularly clear with Lorazepam , which took second place among the most prescribed psychotropic drugs in Germany in 2007, but slipped to 15th place by 2013.

Legal position

The legal situation regarding the individual benzodiazepines depends on the respective benzodiazepine and the respective legislation of the country. In 1984, 33 benzodiazepines were classified as Schedule IV drug by the United Nations Convention on Psychotropic Substances . Midazolam (1990) and Brotizolam (1995) were added later. Flunitrazepam was regrouped to Schedule III in 1995 . Phenazepam (also Fenazepam) is used outside of the European Union and is not in the UN Convention.

Germany

With a few exceptions, benzodiazepines are regulated by narcotics law. In many cases, however, drugs containing benzodiazepines are exempt from the provisions of the Narcotics Prescription Ordinance (“exempt preparations”) up to certain maximum levels and can be prescribed on a normal prescription. For this purpose, the legislature has set maximum quantities per divided form (tablet, suppository , ampoule, volume unit for drops) and / or maximum quantities per pack. These maximum quantities are set individually for each individual active ingredient (e.g. 10 mg per divided tablet unit for diazepam) and are derived from Appendix III to the BtMG. Any additional quantities require a BtM prescription .

North America

In the United States, benzodiazepines require a prescription and are classified as Schedule IV drugs under the Federal Controlled Substances Act . The most commonly used benzodiazepines in the US and Canada are alprazolam and diazepam , followed by clonazepam and lorazepam . In approximately 1.25 million cases of people being admitted to emergency rooms in the United States for drug abuse in 2011, approximately 358,000 cases involved benzodiazepines, predominantly alprazolam (123,750), clonazepam (61,000), lorazepam (43,000), and diazepam (24,000).

Singapore

In Singapore, nimetazepam is classified as a Class C controlled drug .

literature

Web links

Individual evidence

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  2. Kerri Smith: Treating Chronic Pain Without Side Effects In: Der Tagesspiegel , January 2008.
  3. WHO Model List (April 2013). (PDF) (No longer available online.) Archived from the original on December 25, 2014 ; accessed on April 5, 2018 .
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