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Objective: To construct a model for classification of antidepressants on the basis of their binding properties to six common transporter and receptor sites. Design and methods: Receptor binding was quantified by calculating receptor/ transporter occupancy (hereafter: receptor occupancy) for the serotonin (5HT) transporter, norepinephrine (NE) transporter, 5HT2Creceptor, M3receptor, H1receptor and a, receptor. Receptor occupancy has been proven to be an appropriate measure to estimate the pharmacological effects among drugs with the same mechanism of action. To identify groups of antidepressants showing similar patterns of receptor occupancy for different receptors, hierarchical cluster analysis (HCA) and principal component analysis (PCA) were performed. To visualize (a)symmetry between binding profiles of antidepressants, radar plots were used. Results: On the basis of HCA, PCA and the radar plots, four clusters of antidepressants with similar pharmacological properties were identified. The first cluster (sertraline, fluvoxamine, escitalopram, paroxetine, venlafaxine, fluoxetine, Citalopram, duloxetine and clomipramine) included antidepressants with specific affinity for the 5HT transporter. The second cluster (amitriptyline, doxepin and Imipramine) included antidepressants with high affinity for all receptors Investigated. The third cluster (maprotiline, nortriptyline, mianserin and mirtazapine) included antidepressants with high affinity for the NE transporter, H1receptor and 5HT2Creceptor. The fourth cluster (trazodone, nefazodone, reboxetine and bupropion) was identified as group with no specific similarities. Conclusions: The use of the receptor occupancy theory combined with HCA, PCA and radar plots is a useful method to visualize (a)symmetry in binding profiles of antidepressants. It could be a helpful tool in evidence-based practice, selecting the right antidepressant for the right patient, and may be used in pharmacovigilance as a prediction model for adverse effects of novel drugs entering the market.

Objective: To construct a model for classification of antidepressants on the basis of their binding properties to six common transporter and receptor sites. Design and methods: Receptor binding was quantified by calculating receptor/ transporter occupancy (hereafter: receptor occupancy) for the serotonin (5HT) transporter, norepinephrine (NE) transporter, 5HT2Creceptor, M3receptor, H1receptor and a, receptor. Receptor occupancy has been proven to be an appropriate measure to estimate the pharmacological effects among drugs with the same mechanism of action. To identify groups of antidepressants showing similar patterns of receptor occupancy for different receptors, hierarchical cluster analysis (HCA) and principal component analysis (PCA) were performed. To visualize (a)symmetry between binding profiles of antidepressants, radar plots were used. Results: On the basis of HCA, PCA and the radar plots, four clusters of antidepressants with similar pharmacological properties were identified. The first cluster (sertraline, fluvoxamine, escitalopram, paroxetine, venlafaxine, fluoxetine, Citalopram, duloxetine and clomipramine) included antidepressants with specific affinity for the 5HT transporter. The second cluster (amitriptyline, doxepin and Imipramine) included antidepressants with high affinity for all receptors Investigated. The third cluster (maprotiline, nortriptyline, mianserin and mirtazapine) included antidepressants with high affinity for the NE transporter, H1receptor and 5HT2Creceptor. The fourth cluster (trazodone, nefazodone, reboxetine and bupropion) was identified as group with no specific similarities. Conclusions: The use of the receptor occupancy theory combined with HCA, PCA and radar plots is a useful method to visualize (a)symmetry in binding profiles of antidepressants. It could be a helpful tool in evidence-based practice, selecting the right antidepressant for the right patient, and may be used in pharmacovigilance as a prediction model for adverse effects of novel drugs entering the market.

The Netherlands Pharmacovigilance Foundation(Lareb) evaluates the reports as generated by the spontaneous adverse event reporting system. This article describes the adverse event profile of antiepileptic drugs, as well as other drugs that may cause seizures that have been reported to Lareb.

Objective: To collect data of toxicological cases for a 10-year period and to develop a database for comparing epidemiology of intoxications with data from the national poisoning information centre (NVIC) and national prescription data (GIP). Design: Retrospective database study. Methods: All drug intoxications between 1997 and 2006 were identified from the records of the Clinical Pharmaceutical and Toxicological Laboratory in The Hague, Netherlands. Patient demographics and details of drugs analysed were acquired. These data were compared with data from NVIC and GIP. Results and conclusion: Almost 6000 cases were reviewed. From 1997 to 2006 the number of toxicological cases in The Hague increased from 322 to 826 per year. From 2001-2005 >90% of toxicological cases comprised analgesics, antidepressants, antipsychotics and hypnotics. These drugs comprised 60-70% of cases reported to the PIC and 10-12% of prescriptions. Most drug intoxications in The Hague involved analgesics and psychopharmacologic drugs. Relative to prescription data, most intoxications occur with tricyclic antidepressants. There seems to be an imbalance between number of intoxications and prescriptions among SSRIs: citalopram is relatively more involved in intoxications than the other SSRIs, but more research is needed to confirm this.

Objective: To collect data of toxicological cases for a 10-year period and to develop a database for comparing epidemiology of intoxications with data from the national poisoning information centre (NVIC) and national prescription data (GIP). Design: Retrospective database study. Methods: All drug intoxications between 1997 and 2006 were identified from the records of the Clinical Pharmaceutical and Toxicological Laboratory in The Hague, Netherlands. Patient demographics and details of drugs analysed were acquired. These data were compared with data from NVIC and GIP. Results and conclusion: Almost 6000 cases were reviewed. From 1997 to 2006 the number of toxicological cases in The Hague increased from 322 to 826 per year. From 2001-2005 >90% of toxicological cases comprised analgesics, antidepressants, antipsychotics and hypnotics. These drugs comprised 60-70% of cases reported to the PIC and 10-12% of prescriptions. Most drug intoxications in The Hague involved analgesics and psychopharmacologic drugs. Relative to prescription data, most intoxications occur with tricyclic antidepressants. There seems to be an imbalance between number of intoxications and prescriptions among SSRIs: citalopram is relatively more involved in intoxications than the other SSRIs, but more research is needed to confirm this.

The potential for drug-drug interactions in psychiatric patients is very high as combination pharmacotherapy is often used to treat them. In this field, the hepatic cytochrome P450 enzyme system plays a major role. Recently, some new antidepressive and antipsychotic drugs have been introduced on the market. This paper reviews the hepatic metabolism of these new drugs and their potential for drug-drug interactions.

The potential for drug-drug interactions in psychiatric patients is very high as combination pharmacotherapy is often used to treat them. In this field, the hepatic cytochrome P450 enzyme system plays a major role. Recently, some new antidepressive and antipsychotic drugs have been introduced on the market. This paper reviews the hepatic metabolism of these new drugs and their potential for drug-drug interactions.

Hallucinogen persisting perception disorder (HPPD) is a relatively unknown complication of ecstasy use. As a result, the diagnosis is often missed. The prevalence of HPPD is probably low. Few patients seek medical help; HPPD is however widely discussed by drug users on internet fora.We describe a 23-year-old male with HPPD after ecstasy use. Besides visual complaints, including seeing little spots ('visual snow'), the patient suffered from anxiety and depressive symptoms. We treated him with citalopram with good results.In patients with HPPD combined with anxiety or depressive complaints, citalopram could be a good treatment option. Further research into treatment is necessary.

Differentiating panic disorder form epilepsy can be a difficult task. In this case study the task was made more complicated because the patient was being treated with the selective serotonin reuptake inhibitor (SSRI) citalopram which evoked a partial response, thereby delaying the diagnosis of epilepsy. Research results demonstrate that ssris can have not only an antidepressive and calming effect, they can also have an anticonvulsant effect. However, there are also signs that, as this case illustrates, in the long term the anticonvulsant effect can actually convert to proconvulsant effect.

Sexsomnia is a parasomnia characterised by sexual behaviour. A 30-year-old man, with no history of parasomnias or related precipitating factors, developed sexual behaviour during sleep after three weeks of treatment with escitalopram 10 mg daily. The parasomnia disappeared on the sixth day after the escitalopram had been stopped. The temporal relationship between the use of this selective serotonin reuptake inhibitor and the occurrence of the parasomnia suggests a causal relationship, possibly related to increased serotonergic neurotransmission in the raphe nucleus.

The Netherlands Pharmacovigilance Foundation(Lareb) evaluates the reports as generated by the spontaneous adverse event reporting system. This article describes the adverse event profile of antiepileptic drugs, as well as other drugs that may cause seizures that have been reported to Lareb.

Background: We investigated the combination of selective serotonin reuptake inhibitors (SSRIs) with the beta -adrenoceptor/serotonin 1A (5-HT1A) antagonist pindolol, based on the concept that 5-HT1A receptor blockade would eliminate the need for desensitization of presynaptic 5-HT1A receptors and therefore hasten the onset of action and improve the efficacy of SSRIs. However, since pindolol plasma levels after 2.5 mg three times a day are about 60 nmol/L, and the K-i for the 5-HT1A receptor is 30 nmol/L, it is questionable whether pindolol levels in the brain would be sufficient to antagonize 5-HT1A receptors. Using microdialysis in the guinea pig, we correlated brain and plasma levels of pindolol with its capability of augmenting paroxetine-induced increases in brain 5-HT levels. In addition, central beta -receptor antagonism of pindolol was studied by investigating blockade of beta -agonist-induced increases in brain cyclic adenosine monophosphate (cAMP) formation. Methods: Using microdialysis and jugular vein catheterization, we studied the ability of systemically administered pindolol to antagonize central 5-HT1A and beta -adrenoceptors, while simultaneously monitoring pindolol plasma and brain concentrations. Results: Augmentation of paroxetine-induced increases in extracellular 5-HT levels in the ventral hippocampus was only observed at steady stare plasma levels exceeding 7000 nmol/L (concurrent brain levels 600 nmol/L). In contrast, antagonism of beta -agonist-induced increases of brain cAMP levels was already observed at pindolol plasma levels of 70 nmol/L (concurrent brain levels