This communication reviews current literature on lithium augmentation in patients not responding to SSRIs, giving some recommendations at the end. A significant proportion of depressive patients do not respond to a first antidepressive treatment independently of the class of drugs used. During the last 10 years, there have been several case reports published about open and controlled studies on the use of lithium augmentation in patients who were non-responders to SSRIs, including citalopram, fluoxetine, paroxetine and sertraline. The main underlying hypothesis is a synergistic effect between SSRIs and lithium, which both act on serotonergic neurotransmission. The available studies vary considerably in methodology. There are insufficient results available to confirm a rapid improvement (within 24-48h) after introduction of lithium, but most studies show substantial effects after 1 - 2 weeks, and some after 6 weeks. There is as yet no more clear evidence for a pharmacokinetic interaction between lithium and SSRIs with pharmacodynamic consequences. In conclusion, present evidence suggests that a lithium augmentation in depressive patients who do not respond to SSRIs may be an efficacious and generally well tolerated treatment, with a response rate of at least 50% after a period lasting 1 - 2 weeks. However, special care is indicated when treating elderly patients, where the risk of adverse effects is higher.

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St. John's wort extracts are among the most popular herb remedies that have especially been advocated for their favourable side-effect profile. Preliminary data suggest manifold mechanisms of action, such as norepinephrine, serotonine, and dopamine reuptake inhibition, similar to some synthetic antidepressants [1,3]. Hypertension may be an adverse effect of the serotonine, noradrenaline, and dopamine reuptake inhibitor venlafaxine [4]. We report a case of St. John's wort inducing hypertension. The assessment of this case was part of the Arzneimittelsicherheit in der Psychiatrie drug safety program [2].Mr. A, a 56-year-old man without previous psychiatric history and without significant physical particularities, decided to self-medicate with a St. John's wort extract (Ze 117 250 mg b. i. d.) in the context of a stressful personal situation. He had not taken any type of drug since months before and took no other drugs during the hypericum administration. He had never experienced cardiovascular problems, and his blood pressure had always been normal, ranging from 110±120/70±80. After 5 weeks of using this drug, a blood pressure of 160/110 was noticed during a pre-physical training examination. He discussed these findings with his brother, who is a physican. The pressure was monitored for 1 week, at different times of the day, with different devices at home as well as his brother's office. Blood pressure remained between 145±160/95±110 at all measurements. No other side effects were reported or observed. St. John's wort was then discontinued, and his blood pressure normalised after two days, returning and remaining at the usual range of 110±120/70±80. While so far a large of patients have been treated with hypericum extract without any reported effects on blood pressure, the clear temporal association and the lack of alternative explications suggest a causal correlation in our patient. Noradrenaline reuptake inhibition could be the underlying mechanism, as in other noradrenergic antidepressants. Effort should be made to identify and evaluate the relative therapeutic and toxic importance of various extract components. Although in the case of our patient the hypertension was moderate and did not put him at high immediate risk, patients with cardiovascular comorbidities may be at higher risk. This raises question about risks associated with the easy accessibility of such herbal remedies. References1 Di Matteo V, Di Giovanni G, Di Mascio M, Esposito E. Effect of acute administration of hypericum perforatum-CO 2 extract on dopamine and serotonin release in the rat central nervous system. Pharmacopsychiat 2000; 33: 14 ± 18 2 Grohmann R, Rüther E, Engel RR, Hippius H. Assessment of adverse drug reactions in psychiatric in patients with the AMSP drug safety program: methods and first results for tricyclic antidepressants and SSRI. Pharmacopsychiat 1999; 32: 21 ± 28 3 Müller WE, Singer A, Wonnemann M, Hafner U, Rolli M, Schäfer C. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract....

Objective: The newer atypical antipsychotics are prescribed because of their enhanced safety profiles and their larger pharmacological profile in comparison to the conventional antipsychotics. This has led to broad off-label utilisation. The aim of the present survey was to study the prescribing practice of hospital psychiatrists with regard to antipsychotic drugs, comparing patients treated for psychoses or other registered indications to patients receiving off-label antipsychotic treatment. Methods: As part of a pharmacovigilance/pharmacoepidemiology program, all drugs given on 5 reference days (1999-2001) in the 98bed psychiatric hospital of the University of Lausanne, Switzerland, were recorded along with age, sex, and diagnosis. The prescriptions of 202 patients were assessed. Patients were classified in 3 diagnostic groups: (1) patient with psychotic disorders, (2) patients with manic episodes and depressive episodes with psychotic symptoms, and (3) patients with other disorders. Group (1) and (2) formed the class of patients receiving an antipsychotic for a registered indication, and the prescriptions in group (3) were considered as off-label. Results: A lesser number of psychotic patients received antidepressant (p<0.05) and nonbenzodiazepine hypnotics (p<0.001) compared to the patients of the other two groups. The patients with affective disorders seldom received a combination of an atypical and a conventional antipsychotic, whereas a lesser number of patients with offlabel indications received atypical antipsychotics less often than those of the two comparison groups (p<0.05). Stepwise logistic regression revealed that patients with a psychotic disorder were more likely to receive an antipsychotic medication in medium or high doses (p<0.001), in comparison to the two other groups. Conclusion: The new antipsychotic drugs seem to be prescribed with less hesitation and mainly for approved indications. Physicians prescribed new drugs, off-label , only after having gained some experience in the field of the approved indications, and were more cautious with regard to doses when treating on an offlabel basis.

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