"Articles of interest"
Compiled by Denise Duncan, BPharm, DipPharmPrac, MRPharmS, Senior Drug Information Pharmacist, Bethlem and Maudsley NHS Trust
A guide to the safety of CNS-active agents during breastfeeding.
Chisholm CA, Kuller JA., Drug Safety 1997; 17: 127-142
In psychiatry we are often faced with the dilemma of which psychotropic to recommend for depression, psychosis or bipolar illness when the patient is known to be breastfeeding. This timely review summarises available data on antidepressants, antipsychotics, opiates, benzodiazepines and anticonvulsants and actually makes recommendations. I recommend you order this article from your library.
Pharmacokinetic interactions involving clozapine.
Taylor D., British Journal of Psychiatry 1997; 171:109-112
As we learn more about the cytochrome p450 system, it is becoming possible to understand and predict drug interactions. In this article the metabolism of clozapine is thoroughly examined, with existing drug interactions reviewed vis-à-vis the cytochrome p450 system and predictions made as to what drugs might be expected to interact. Taylor concludes that compounds which induce CYP1A2 (carbamazepine, tobacco smoke, barbecued food) may reduce plasma clozapine levels whereas inhibitors and substrates of this isoenzyme (caffeine, erythromycin, ciprofloxacin) may increase levels. There have also been reports of interaction with inhibitors of CYP2D6, but further research is imperative in this growing area to elucidate these findings.
Novel alternatives and supplements to lithium and anticonvulsants for bipolar affective disorder.
Dubovsky SL, Buzan RD., Journal of Clinical Psychiatry 1997; 58: 224-242
In this review, treatments including ECT, calcium channel blockers, benzodiazepines, antipsychotics, thyroid hormones, psychosurgery, lamotrigine and gabapentin are discussed with respect to efficacy and rationale. Unfortunately, large controlled trials are generally lacking and so it is difficult to know what the ideal role is for each of these drugs. Like the standard therapies however most of these treatments appear to be more effective at preventing mania than depression.
Choice of neuroleptics in epilepsy.
McConnell H, Duncan D, Taylor D., Psychiatric Bulletin 1997, 21: 642-645
Tardive dyskinesia - how is it prevented and treated?
Duncan D, McConnell H, Taylor D., Psychiatric Bulletin 1997, 21: 422-425
I think people will find this two articles useful. The first is the only article I am aware of that reviews all antipsychotics with respect to seizure threshold and epilepsy. The second is a general review article on tardive dyskinesia.
Paroxetine withdrawal syndrome in a neonate.
Dahl ML, Olhager E, Ahlner J., British Journal of Psychiatry 1997, 171: 391-392
A mother who began paroxetine 30mg/d during the sixth month of pregnancy gave birth to a baby at 39 weeks. The pregnancy was normal and there were no complications at delivery. Twelve hours later the baby had an increased respiratory rate and jitteriness and within a few hours had developed a tremor and increased muscle tone. These symptoms resolved over the next few days apart from the jitteriness, which resolved in the baby at the age of four weeks. Similar reports have been noted with fluoxetine and sertraline. It may be that like tricyclic antidepressants, the dose of SSRIs should also be reduced slowly and stopped before delivery.
Augmentation of clozapine therapy with ondansetron.
Briskin JK, Curtis JL., Am J Psych 1997; 154(8):1171
This case describes a 31-year old male who, after receiving up to 900mg of clozapine for over 3 years, still suffered from delusions, hallucinations and thought disorder. After a diagnosis of Hodgkins Lymphoma was made and chemotherapy and ondansetron (a selective 5HT3 antagonist) was commenced, it was noted that he had fewer delusions and hallucinations. During this time, he was on clozapine 75mg/day, valproate, Vitamin E, insulin, glyburide, ferrous sulphate and cisapride.Two weeks after chemotherapy finished, his symptoms returned to previous levels. Ondansetron, 4mg bd, was therefore introduced and after two weeks there was marked improvement, which had persisted by week 10. The authors do not believe that ondansetron had increased clozapine's plasma levels (although these were not taken), but that it was effective in augmenting the clinical effects of clozapine.
Reduced morbidity after gradual discontinuation of lithium treatment for bipolar 1 & 11 disorders: a replication study.
Baldessarini RJ, Tondon L, Floris G, Rudas N. Am J Psych 1997; 154(4): 551-553.
As pharmacists, we are often asked how quickly lithium should be discontinued. In this study, patients with bipolar 1 or 11 who had been receiving lithium for longer than 1 year and who had achieved at least a 75% reduction in the time they were ill, had their lithium discontinued either rapidly (over 1-14 days) or gradually (15-30 days). At 2 years follow-up, 30.7% of the patients who had been withdrawn from lithium gradually had not relapsed, compared with only 4.9% of the rapid discontinuation group. Also, the time to 50% risk of recurrence for the gradual and rapid discontinuation groups was 14 months and 2.5 months respectively. This therefore suggests that morbidity may be reduced when lithium is reduced gradually.
Lithium: evidence reconsidered.
Moncrieff J. Br J Psych 1997; 171: 113-119
Lithium: balancing risks and benefits.
Cookson J. Br J Psych 1997; 171: 120-124
In the first review, the author examines the evidence behind the recommendations for lithium's use in the treatment of acute mania, prophylaxis of bipolar disorder and augmentation therapy for acute depression. Lithium's adverse effects are also considered. She concludes that much of the data may be biased or results from studies with methodological flaws and that there is in fact little evidence to suggest that lithium is effective in these conditions. Conversely, Cookson, in his article, addresses the issues raised by Moncrieff and states, in his conclusion, that there is sufficient evidence to justify the use of lithium in acute mania and the prophylaxis of bipolar disorder. He also gives guidelines as to which patients may be more likely to benefit from lithium.
Treatment of acute mania with gabapentin
Stanton SP, Keck PE, McElroy SL American Journal Psychiatry 1997; 154(2): 287
This letter reports a dramatic improvement in manic symptoms in a 40 year old white man with DSM-IV bipolar I disorder and alcohol dependence. A dose of 900mg gabapentin was given on day 1 and then increased by 900mg a day until a dose of 3600mg was reached. This dose is obviously large and is above the maximum BNF dose for epilepsy in the UK. It is, however, a commonly used dose in the USA. Gabapentin may prove to be yet another anticonvulsant which is effective in mania.
See also Gabapentin in the Treatment of Bipolar Disorder.
American Journal Psychiatry 1997; 154:291-292.
Venlafaxine Withdrawal Reactions
Louie AK, Lannon RA, Kirsch MA, Lewis TB, American Journal of Psychiatry (1996) 153:1652.
Like other antidepressants, venlafaxine has been associated with a withdrawal reaction. In this letter three cases are presented. Withdrawal reactions occurred within three days of stopping or decreasing the dose and included nausea, chills, fatigue, urinary frequency, bizarre dreams, dizziness, shock-like sensations, diarrhoea and auditory hallucinations. In order to avoid these effects the dose should be tapered over 1-4 weeks.
Management Of Zolpidem Withdrawal
Watsky E, Journal of Clinical Psychopharmacology (1996) 16: 459.
Attempted zolpidem withdrawal after three months therapy in this 50 year old man resulted in symptoms including hyperventilation, cramps, angry feelings and shallow breathing. Diazepam was given to facilitate withdrawal from zolpidem, before being withdrawn itself over 10 days.
Worsening of Psychosis with Clozapine and Selective Serotonin Reuptake Inhibitor Combination : Two case Reports.
Chong SA, Tan CH, Lee HS, Journal of Clinical Psychopharmacology (1997) 17 (1): 68-69.
The authors postulate that a therapeutic window for clozapine exists. In both cases the addition of SSRIs raised clozapine plasma levels and a worsening of psychosis ensued. Alternative explanations include that the addition of SSRIs caused an imbalance between 5HT and dopamine blockade or that high plasma clozapine levels resulted in a toxic psychosis caused by clozapine's potent anticholinergic activity.
Discontinuation rates of SSRIs and tricyclic antidepressants: a meta-analysis and investigation of heterogeneity
Hotopf M, Hardy R, Lewis G, British Journal of Psychiatry (1997), 170: 120-127.
This meta-analysis looked at rates of discontinuation of older tricyclics (amitriptyline, imipramine) compared to newer tricyclics (dothiepin, nortriptyline, desipramine, clomipramine, doxepin), heterocyclics and SSRIs. The type of tricyclic or heterocyclic compound had not previously been controlled for in other meta-analyses. The authors conclude that SSRIs are not less likely to be discontinued when compared with the newer tricyclics or heterocyclics.
Effects of antidepressant drugs on sexual function
Baldwin DS, Thomas SC, Birtwistle J. International Journal of Psychiatry in Clinical Practice 1997; 1:47-58.
Here is a useful article on sexual dysfunction associated with antidepressants. The authors discuss possible mechanisms and treatments as well as reporting on the sexual adverse effects that have occurred with the different groups of antidepressants. They also mention what little work there is comparating different antidepressants. Interesting reading.
Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial.
Tollefos GD, Beasley Jr CM, Tran PV et al. American Journal of Psychiatry 1997; 154(4):457-465.
In the largest trial involving a neuroleptic to date, 1,996 patients were randomly assigned to treatment with either olanzapine (n=1336) or haloperidol (n=660) for six weeks. Patients were started on a 5mg dose of either drug and this was titrated by 5mg/week to 20mg/day. Interestingly the most common olanzapine dose was 20mg/day (31%) while the most common haloperidol dose was only 5mg/day (37%). The olanzapine group had greater improvements in the BPRS, PANSS, CGI, and the Montgomery Asberg Depression rating scale. Adverse events reported more frequently with olanzapine included excessive appetite (24% vs 12.4%) and a dry mouth (22.2% vs 16.2%). Dystonia, parkinsonism and akathisia were however reported significantly less often than with haloperidol. Olanzapine appears to offer significant advantages over haloperidol for both efficacy and tolerability but at a cost.
See also Negative Symptoms: A Path Analytic Approach to a Double-Blind, Placebo- and Haloperidol-Controlled Clinical Trial with Olanzapine. American Journal of Psychiatry 1997;154:466-474.
Rapid anaesthetic-antagonist detoxification of heroin addicts: What origins, evidence base and clinical justification?
Gossop M, Strang J. British Journal of Intensive Care 1997;7(2):66-69.
Approximately 5,000-10,000 heroin misusers are believed to have been treated by giving opiate antagonists during anaesthesia. This has led to wide spread interest. In this article, the authors present the history of antagonist precipitated detoxification with respect to the different treatment options employed during the years. They also discuss the possible advantages and disadvantages of the treatment.
Elevated serum phenytoin concentrations associated with co-administration of sertraline.
Haselberger MB, Freedman LS, Tolbert S. Journal of Clinical Psychopharmacology 1997;17(2):107-109.
This brief report described two patients whose phenytoin levels increased dramatically after the addition of sertraline. These are the first reports of such an interaction. In a previous unpublished double-blind placebo trial, no interaction was noted. As the interaction now seems possible, phenytoin levels should be monitored closely after the addition of sertraline.
