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PubMed1989

Responses of substantia nigra pars reticulata neurons to benzodiazepine ligands after acute and prolonged diazepam exposure. I. Modulation of gamma-aminobutyric acid sensitivity.

We have examined the ability of the benzodiazepine inverse agonist, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), and the antagonist, Ro15-1788, to modulate gamma-amino-butyric acid (GABA) sensitivity of reticulata neurons after chronic (3 week) and acute (1 hr) diazepam exposure. Sensitivity to GABA was analyzed by monitoring single unit responses to microiontophoretically applied GABA. The inverse agonist DMCM decreased GABA sensitivity of reticulata neurons to similar levels in control, chronic diazepam and acute diazepam-treated groups. Ro15-1788 administration reversed the effects of DMCM on GABA sensitivity and also resulted in comparable levels of GABA sensitivity in all treatment groups. Thus, the ability of the inverse agonist DMCM and the antagonist Ro15-1788 to alter GABA sensitivity of reticulata neurons was not altered by diazepam treatment. However, reticulata GABA sensitivity in the absence of additional benzodiazepine ligands was enhanced in both acute and chronic diazepam groups when compared to control values. The similarity in reticulata responses after both chronic (3 week) and acute (1 hr) diazepam treatments suggests that the enhanced sensitivity to GABA merely reflects the presence of diazepam. Thus, the ability of diazepam to potentiate reticulata GABA responses does not show time-dependent changes with prolonged benzodiazepine exposure.

Animals↗
PubMedDate not supplied

[Intro- and extraversion in patients with neuroses as factors differentiating the effect of diazepam on psychomotor function].

The influence of various diazepam doses on selected psychomotor functions in neurotic patients was studied with regard to introversion and extraversion. The group consisted of 110 patients randomly selected into diazepam group (60 cases) and placebo group (50 subjects). In each group introvertics (24 treated with diazepam and 13 with placebo) as well as extravertics (15 subjects receiving diazepam and 12 placebo) were selected. Further analysis excluded 36 ambivertics. Results did not suggest substantial dependence between introversion and extraversion, and effect of diazepam on psychomotor functions. Only the negative effect of certain diazepam doses on visualmotor coordination in introvertic patients, as well as such influence on time of reaction with choice was found. It regards to diazepam doses of 10 mg t.i.d. after 7-10 days of treatment, and also the influence of single dose of 10 mg diazepam after 3-4 hours on visual-motor coordination as well.

Adolescent↗
PubMed1986

Effects of diazepam and midazolam on baroreflex control of heart rate and on sympathetic activity in humans.

The effects of induction of anesthesia with diazepam and midazolam on baroreflex control of heart rate and on plasma levels of catecholamines were investigated in this study. Group 1 subjects (n = 10) received diazepam, 0.4 mg/kg. Group 2 subjects (n = 10) received midazolam, 0.3 mg/kg. Baroreflex function was assessed using a pressor test (phenylephrine). In addition, samples for subsequent determination of plasma norepinephrine and epinephrine levels and plasma diazepam or midazolam concentrations were collected before and 5, 10, and 15 min after intravenous drug administration. The pressor baroreflex slope declined significantly after diazepam or midazolam administration with the maximal changes (-45 and -43%, respectively) observed when plasma diazepam or midazolam concentrations were the highest. Norepinephrine plasma concentrations decreased at each measurement with both drugs. In contrast, epinephrine concentration decreased only after midazolam. The authors conclude that diazepam or midazolam used for induction of anesthesia results in a transient depression of baroreflex function and a sustained decrease of sympathetic tone. This study also indicates that the depression of arterial baroreflex heart rate responses under diazepam or midazolam anesthesia are less pronounced than the depression of baroreflex responses reported by other investigators with potent inhalational anesthetics. However, this disruptive effect of diazepam and midazolam on sympathetic control of circulation might induce a limited ability to compensate for hemodynamic alterations related to hypovolemia.

Adult↗
PubMed1985

Differential diazepam-antagonist effects of the benzodiazepine receptor ligand CGS 9895 in rodents.

CGS 9895, a pyrazoloquinolone benzodiazepine receptor ligand, was administered alone and concomitantly with diazepam in order to assess its agonist and diazepam-antagonist properties on various behaviors in rodents. In mice, CGS 9895 neither potentiated nor blocked the convulsant effects of pentylenetetrazole. However, doses of 3.0 and 10 mg/kg of CGS 9895 i.p. produced dose-related antagonism of the anticonvulsant effects of diazepam against pentylenetetrazole (80 mg/kg i.p.). In rats, diazepam produced dose-related increases in ataxia as measured on the rotarod. CGS 9895 (0.3-10 mg/kg i.p.) was without effect on performance on the rotarod, but produced dose-related parallel shifts to the right in the diazepam dose-effect curve. Also in rats, behavior was maintained under a multiple schedule where in one component every 20th response resulted in water presentation (unpunished behavior) and in a second component every 20th response resulted in both shock and water presentation (punished behavior). CGS 9895 (0.3-30 mg/kg i.p.) was without significant effect on either punished or unpunished responding. Increasing doses of diazepam (0.1-10 mg/kg p.o.) first increased and then decreased rates of punished responding but only decreased rates of unpunished responding. CGS 9895 (3.0 mg/kg i.p.) neither potentiated nor antagonized diazepam. In another group of rats, behavior was maintained under a multiple fixed-interval 5 min fixed-ratio 20 response schedule of water presentation. CGS 9895 (0.3-30 mg/kg i.p.) did not affect performance under this schedule. Diazepam (0.3-30 mg/kg p.o.) primarily decreased rates under the fixed-ratio schedule, but increasing doses first increased and then decreased rates under the fixed-interval schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Validation of a radioreceptor assay technique for monitoring pharmacological active material during intensive diazepam tetanus therapy.

The present study's aim was to monitor the daily plasma levels of diazepam and its metabolites in two tetanic patients who were receiving very strong doses of diazepam in continuous infusion. The kinetics of high doses of diazepam were estimated. These plasma levels were determined selectively using gas-liquid chromatography (GLC), then correlated with a global estimation by radioreceptor-assay (RRA). At the end of the infusion, the kinetics of diazepam and of RRA active material were calculated using a linear, open, two compartment model. Muscle-relaxant and residual sedative effects were clinically monitored. The mean concentrations of diazepam (2.33, 0.60 micrograms/ml), desmethyldiazepam (3.27, 1.00 micrograms/ml) and oxazepam (0.73, 0.47 micrograms/ml) estimated by GLC and of RRA active material (5.62, 1.08 micrograms/ml) correlated better when active metabolites were considered (r = 0.898) than when diazepam alone was taken into account (r = 0.730), indicating that these metabolites influence the overall activity of the parent compound. Half-lives of RRA results (52.6 h for patient 1 and 82.5 h for patient 2) were higher than those of diazepam estimated using GLC results (21.2 h for patient 1 and 42.3 h for patient 2). This could be related to the contribution of the active metabolites and might explain the residual sedative effect observed for at least seven days following cessation of the diazepam (DZP) infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotransformation↗
PubMedDate not supplied

A comparison of oral and intravenous diazepam sedation for periodontal surgery.

Intravenous and oral diazepam were evaluated as to their effectiveness in conscious sedation during two similar surgical episodes. Ten patients, six females and four males, from 30 to 60 years of age were included in the study. Patients received either 10 mg oral diazepam and saline intravenous injection or oral placebo and 10 mg intravenous (IV) diazepam at each trial. Half the patients received the oral diazepam first and the other half received the IV diazepam first. Patients were not informed as to the route of administration during each trial. Physiologic stress was measured by monitoring blood pressure, heart rate, skin temperature, galvanic skin response, and plasma catecholamine levels. Patients evaluated their comfort and nervousness levels on a questionnaire. Anterograde amnesia was tested by patient's ability to recall objects shown them during the procedure. As evidenced by the physiologic and biochemical parameters, intravenous diazepam was more effective in reducing anxiety and stress as compared with an equivalent oral dose. Patients' subjective ratings were consistent with these findings. Intravenous diazepam was effective in producing anterograde amnesia in the majority of patients, whereas no amnesic effect was noted with oral diazepam. Correlation statistics demonstrated a relative independence of the parameters measured in the present study indicating that all parameters must be considered in overall patient evaluation. Reduction of anxiety during the first surgery resulted in less anxiety on the subsequent visit.

Administration, Oral↗
PubMed1983

Diazepam versus lorazepam: relationship of drug distribution to duration of clinical action.

Eight healthy volunteers received single intravenous doses of diazepam and lorazepam on two separate occasions. Kinetic parameters of drug distribution and clearance were determined by measurement of multiple plasma concentrations following each dose. Elimination half-life for diazepam averaged 51.2 hr, as compared with 15.7 hr for lorazepam. However, after correction for individual differences in protein binding (mean free fraction 1.5% for diazepam versus 10.1% for lorazepam), the volume of distribution of unbound diazepam (mean 133 liter/kg) was more than 10 times larger than that of lorazepam (mean 12 liter/kg). This is consistent with in vivo measurements of lipid solubility indicating that diazepam has a much larger octanol/water partition coefficient than lorazepam. Thus, the shorter duration of action of a single intravenous dose of diazepam as compared with lorazepam, despite the much longer half-life of diazepam, is explained by the more extensive tissue distribution of unbound diazepam.

Adult↗
PubMed1978

[Effects of diazepam on evoked potential recorded from basal medial amygdaloid nucleus, lateral hypothalamus and midbrain reticular formation (author's transl)].

The evoked potential in the lateral hypothalamus (LH) recorded by stimulation of basal medial amygdaloid nucleus (Abm) showed a triphasic pattern and diazepam (2 mg/kg, i. p.) decreased the late component. The evoked potential in the midbrain reticular formation (MRF) recorded by stimulation of Abm showed a fast component with a relatively short latency followed by a biphasic late component and diazepam decreased the late component. Though the evoked potential in the Abm recorded by stimulation of LH showed a triphasic pattern, diazepam had no influence on the amplitude. Diazepam increased markedly the amplitude of evoked potential in the MRF recorded by stimulation of LH. Diazepam was ineffective on the evoked potential in the Abm recorded by stimulation of MRF. Diazepam decreased markedly the late component of evoked potential in the LH recorded by stimulation of MRF. These results suggest that the depression of emotional behavior by diazepam may be particularly related to the fact that the evoked potential in the LH recorded by stimulation of Abm was decreased by diazepam.

Amygdala↗
PubMed1982

[Changes in central nervous system development in rats caused by chronic administration of diazepam during the suckling period].

Wistar-Imamichi male rats were treated daily with diazepam (s.c.) in a dose of 0.2, 2, 5 mg/kg (D0.2-, D2- or D5-rats) or 5%EtOH, beginning on the 8th day until the 20th day after birth. 1) The developmental pattern of the coordinated motor activity in D-rats did not show any significant alteration from that in controls. 2) D2- and D5-rats showed a significant decrease in the activity counts of ambulation and rearing at 16 and 19 days of age in the open-field test. With acute administration of 0.5 mg/kg diazepam (i.p.) at 20 days of age, however, the decrease in the counts of ambulation and rearing was significantly lower in D-rats than that in normal- and 5%EtOH-rats. 3) At 5 weeks of age, the effect of acutely administered diazepam (2 mg/kg, i.p.) was also less marked in D-rats. Incidences of ataxia by diazepam were 71.4% in D0.2, 33.3% in D2-rats and 88-100% in controls at 10 min. Thirty min later, none of the D-rats showed ataxia. 4) At 7 weeks of age, there was no significant difference in the response to acute diazepam administration among the groups. No effect of diazepam on the body growth and the time of eye-opening was detected. The present results indicate that chronic treatment with rather small doses of diazepam during an infantile period in the rat induces a long-lasting tolerance to diazepam.

Animals↗
PubMed1980

Effect of diazepam on the lower esophageal sphincter. A double-blind controlled study.

The effect of diazepam on the lower esophageal sphincter (LES) pressure was studied in a controlled randomized double-blind protocol. Twenty-five patients received intravenous saline, diazepam 5 mg. and diazepam 10 mg. on different days. Diazepam 5 mg. and diazepam 10 mg. caused a mean peak reduction in LES pressure of 18.9 and 37.8% respectively. The peak reduction in LES pressure was dose-related and lasted approximately seven minutes. Awareness of diazepam's ability to significantly lower LES pressure is needed to avoid the possibility of falsely diagnosing reflux by endoscopy. The mechanism whereby diazepam lowers LES pressure is not known, however, diazepam may be acting as a smooth muscle relaxant since myogenic influences have been implicated in the genesis of LES pressure.

Adult↗
PubMed1995

Diazepam, given postischemia, protects selectively vulnerable neurons in the rat hippocampus and striatum.

Following cerebral ischemia, certain populations of neurons degenerate. Excessive accumulation of excitatory amino acids in the synaptic cleft, activation of excitatory amino acid receptors, and influx of calcium into neurons play a key role in the development of ischemia-induced neuronal death. We hypothesized that neuroprotection may be achieved by enhancing inhibitory (i.e., gamma-aminobutyric acid, GABA) neurotransmission to offset excitation. Diazepam, a drug that increases GABA-induced chloride channel opening, was administered (10 mg/kg, i.p.) to rats 1 and 2 hr following 15 min of transient global ischemia, when hippocampal GABA levels, increased during ischemia, returned to basal. Rats were maintained normothermic during ischemia and became hypothermic following the injections of diazepam. Four days later, rats were sacrificed and the brains were examined for neuronal degeneration and the presence of GABAA receptors labeled by 35S-t-butylbicyclophosphorothionate (35S-TBPS). There was substantial neuroprotection of striatal neurons and pyramidal neurons in the CA1 area of the hippocampus. In addition, diazepam prevented the loss of 35S-TBPS binding sites in the striatum and in the dendritic fields of the CA1 hippocampus following ischemia. Since hypothermia, itself, is neuroprotective, we determined if hypothermia was required for the ability of diazepam to produce neuroprotection. Diazepam was microinjected into the CA1 hippocampus 1 and 2 hr following ischemia, and rats remained normothermic. Four days later, diazepam still produced substantial protection of hippocampal neurons. Thus, postischemic hypothermia may have contributed to the neuroprotection by diazepam when it was administered systemically, but the neuroprotective effect of diazepam did not require hypothermia. We conclude that delayed enhancement of GABAergic neurotransmission directly at the site of vulnerability following an ischemic event protects the vulnerable neurons from death.

Animals↗
PubMed1993

Efficacy of diazepam and avizafone against soman-induced neuropathology in brain of rats.

The purpose of this investigation was to compare the efficacy of diazepam and a water soluble pro-diazepam drug, avizafone (lysyl, peptido-aminobenzophenone diazepam pro-drug) in preventing or reducing the severity of soman-induced neuropathology in rats and to determine the temporal relationship between seizure initiation, anticonvulsant administration and the incidence and severity of soman-induced neuropathology. Brains from rats, treated with a convulsant dose of soman (pinacolyl methylphosphonofluoridate) and anticonvulsants such as diazepam and avizafone, were evaluated by light microscopy for evidence of neuropathology. All rats received atropine methyl nitrate (20 mg/kg, ip)+the bispyridinium acetylcholinesterase reactivator HI-6 (125 mg/kg, ip; 1-(((4-(aminocarbonyl)pyridinio) methoxy)methyl)-2-((hydroxyimino)methyl)-pyridinium dichloride) in the same solution 10 min before soman (130 micrograms/kg,sc). Three days later the rats were perfused and the tissue fixed for histological evaluation. Necrosis and/or malacia (degenerative changes) and hemorrhage were observed in some groups. The sites where pathology was most frequently observed and with greater severity were the piriform cortex, amygdala and (dorsal) thalamus. Less severe changes were observed in the cerebral cortex and hippocampus. There were no changes in the hypothalamus. Diazepam given 10 minutes before soman prevented the occurrence of soman-induced convulsions and neuropathology (i.e. degenerative changes were not then seen). Diazepam given at the start of the soman-induced convulsions reduced considerably the convulsions and the degree of neuropathology. Avizafone given 10 minutes before soman reduced slightly the effect of soman. Other treatments (diazepam given 30, 60 and 120 minutes after the start of the convulsions and avizafone given at the start of convulsions) showed little or no effect on the neuropathology associated with soman administration. The results of this study have demonstrated that the use of an anticonvulsant, such as diazepam, must be initiated shortly after soman exposure in order for any therapeutic benefit to be realized.

Animals↗
PubMedDate not supplied

Effects of diazepam and the specific benzodiazepine antagonist flumazenil on somatosensory evoked potentials in rats.

Changes in somatosensory evoked potentials were studied in 88 rats following intravenous injections of diazepam (0.5, 1 and 5 mg/kg) and flumazenil (0.5 and 5 mg/kg). The antagonist effect of flumazenil against previously administered diazepam was evaluated by somatosensory evoked potentials, when given in the same doses. Generally, a peak-latency increase and an amplitude reduction were observed after diazepam administration. The low dose of flumazenil led to similar changes in somatosensory evoked potentials. The higher dose of flumazenil resulted in an immediate, short-lasting latency decrease of the late cortical potentials and an amplitude reduction with a delay in its appearance. According to the obtained data, diazepam elicited a marked suppressive action mainly on the corticocortical processing of the sensor information with a milder effect on the thalamic level. Flumazenil showed some intrinsic activities with the low dose effects being benzodiazepine-like and the higher dose resulting in two overlapping opposite actions (initially stimulant and subsequently suppressive). The same flumazenil doses, applied 30 min after injection of diazepam, were able to fully or partially reverse (with some dose differences) the diazepam-induced latency prolongations, whereas flumazenil could not antagonize significantly the diazepam effect on the amplitudes. This may be due to the greater influence of diazepam on the amplitudes.

Animals↗
PubMedDate not supplied

Diazepam, adenosine analogues and calcium channel antagonists inhibit the contractile activity of the mouse urinary bladder.

The main neurotransmitter of the mouse urinary bladder is ATP, which is hydrolyzed to AMP and adenosine; the latter compound, in contrast to ATP, relaxes the smooth muscle. Diazepam also relaxes the urinary bladder and, since some peripheral and central effects of the benzodiazepines are thought to be induced by inhibition of adenosine uptake or by inhibiting calcium channels, the effects of diazepam, adenosine, R-phenylisopropyladenosine, cyclohexyladenosine, and of the calcium channel antagonists, diltiazem, verapamil and nifedipine, were studied on the contractile responses of the mouse isolated urinary bladder. The contractile responses of the bladder's smooth muscle were elicited by transmural stimulation and by application of ATP or acetylcholine. All drugs mentioned decreased the contractile responses of the bladder. The inhibitory effect of diazepam was similar to that induced by adenosine, R-phenylisopropyladenosine, cyclohexyladenosine, and nifedipine. 8-Phenyltheophylline, an adenosine receptor antagonist, did not decrease the relaxatory response of diazepam, which might exclude a P1 purinoceptor-mediated mechanism in the response studied. Diazepam did not significantly change the inhibitory effects of diltiazem and nifedipine on the contractile response to acetylcholine. The similar patterns of relaxant effects, exerted by diazepam, adenosine analogues and calcium channel antagonists, suggest the interference of benzodiazepine, and adenosine and its analogues on calcium channels of the urinary bladder smooth muscle. The inability of diazepam to further increase the effects of diltiazem and nifedipine on the responses to acetylcholine, reinforces the hypothesis that diazepam is acting through a common mechanism with calcium antagonists.

Acetylcholine↗
PubMed1997

Stimulatory effect of diazepam on gastric acid secretion in the continuously perfused stomach in rats under urethane anesthesia.

The effects of diazepam, a typical benzodiazepine receptor agonist, on gastric acid secretion were studied in both conscious pylorus-ligated rats and the perfused stomach of rats under urethane anesthesia. Diazepam did not affect acid secretion in conscious pylorus-ligated rats. Under urethane anesthesia, diazepam showed a definite stimulation on gastric acid secretion. However this stimulatory action was caused neither by 4'-chlordiazepam, which is a peripheral benzodiazepine receptor agonist, nor beta-carbline-3-carboxylic acid methyl ester, which is an inverse benzodiazepine receptor agonist. Pretreatment with atropine, hexamethonium or bilateral truncal vagotomy inhibited the diazepam-induced acid secretion. Pretreatment with flumazenil, which is a benzodiazepine receptor antagonist, reduced the acid secretion induced by diazepam, but pretreatment with 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide, which is a peripheral benzodiazepine receptor antagonist, did not reduce the acid secretion induced by diazepam. 3-Mercaptopropionic acid, which is an inhibitor of GABA biosynthesis, picrotoxin and pentylenetetrazol inhibited diazepam-stimulated acid secretion. Gastric acid secretion stimulated by baclofen was not affected by flumazenil, 3-mercaptopropionic acid or picrotoxin. These results suggest that acid secretion is centrally stimulated by diazepam in rats under anesthesia, and the stimulatory action is closely associated with benzodiazepine-GABA complex receptors.

3-Mercaptopropionic Acid↗
PubMed1989

Cerebral blood volume and CSF pressure following administration of ketamine in dogs; modification by pre- or posttreatment with hypocapnia or diazepam.

The effects of ketamine (2 mg/kg) on cerebral blood (CBV) and cerebrospinal fluid (CSF) pressure, and the modification of ketamine's effects by pre- or posttreatment with hypocapnia (PaCO2 of 20-25 mm Hg) or diazepam (0.3 mg/kg) were determined in 26 dogs. In Group I (n = 7), the sequence of experimental treatments was as follows: control, ketamine, hypocapnia, and normocapnia. In Group II (n = 7), the sequence was control, hypocapnia, ketamine, and normocapnia. In Group III (n = 6), the sequence was control, ketamine, and diazepam. In Group IV In (n = 6), the sequence was control, diazepam, and ketamine. Ketamine alone increased CBV by 11.7 +/- 6.6 (Group III) to 12.4 +/- 6.9% (Group I) (mean +/- SD) and increased CSF pressure by 6.0 +/- 3.9 (Group I) to 10.7 +/- 5.2 (Group III) cm H2O. Pretreatment with hypocapnia or diazepam reduced CSF pressure and CBV so that when ketamine was administered after 15 min of hypocapnia or diazepam, CSF pressure and CBV rose only to prehypocapnia or prediazepam levels. When hypocapnia or diazepam were administered 15 min after ketamine, CSF pressure and CBV decreased to preketamine levels. For all treatments, CSF pressure changed in parallel with CBV in the absence of significant changes in PaCO2, expired CO2, or mean arterial blood pressure (except for a decrease of mean arterial blood pressure with diazepam pretreatment). We conclude the following: (a) ketamine increases CBV concomitant with increases in CSF pressure, (b) ketamine increases CBV and CSF pressure independent of significant change in PaCO2, and (c) pre- or posttreatment with hypocapnia or diazepam reverses ketamine-induced increase of CBV and CSF pressure in dogs with normal CSF pressure and no cerebrovascular damage.

Journal Article↗
PubMed1983

Long v short half-life benzodiazepines in the elderly. Kinetics and clinical effects of diazepam and oxazepam.

Oxazepam and diazepam were compared in healthy elderly volunteers. Absorption of diazepam was faster than oxazepam and onset of clinical effects were more profound. Diazepam accumulation was extensive, washout was slow and active compounds were present two weeks after the last dose. Oxazepam accumulation was significantly less and elimination significantly faster than diazepam. There was no difference between oxazepam and diazepam in sedation or fatigue during the drug treatment, but sedative effects persisted for two weeks after diazepam therapy was discontinued. Sedation rapidly returned to baseline in the oxazepam group. Thus, the differing pharmacokinetic profiles of diazepam and oxazepam have clinical consequences during multiple dosage in the elderly.

Age Factors↗
PubMed2003

Efficacy of diazepam as an anti-anxiety agent: meta-analysis of double-blind, randomized controlled trials carried out in Japan.

Diazepam is one of the most widely used, broad-spectrum anti-anxiety agents. The aim of this study was to evaluate the efficacy of diazepam, and to establish whether it is more effective than a placebo in improving the various neurotic anxiety states seen in patients with neurosis or psychosomatic disease. Of the recently established comprehensive register of psychotropic drug trials carried out in Japan, a total of 17 double-blind, randomized controlled trials were identified on the treatment of neurosis using anti-anxiety compounds, in which both diazepam and placebos were used. Meta-analysis of these 17 studies demonstrated that diazepam is significantly more effective than a placebo (relative risk 1.35, 95% confidence interval 1.21-1.51, number needed to treat 9). The maximal effective dose of diazepam seems to be 12 or 18 mg/day with a treatment duration of 2 or more weeks. There was no significant difference between the effects of placebo and a diazepam dose of 6 mg/day. Caution should be exercised in assessing these results, however, since this is the first meta-analysis showing the significant effectiveness of diazepam in the treatment of neurosis or psychosomatic disease.

Anti-Anxiety Agents↗