TITLE:   Adverse reactions of selective serotonin reuptake inhibitors: reports from a spontaneous reporting system.
AUTHOR:  Spigset, O.
  Adverse Drug Reactions Monitoring Center, Division of Clinical Pharmacology,
Norrland University Hospital, Umea, Sweden. Olav.Spigset@relis.rit.no 
JOURNAL: Drug Safety; VOL 20, ISS 3, 1999, P277-87.
PY: 1999

AB: OBJECTIVE: The selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) are extensively used in the treatment of depression, panic disorder and obsessive-compulsive disorder, and are now being evaluated in the treatment of a number of other psychiatric disorders. The aim of this study was to investigate the 
pattern of adverse reactions reported on SSRIs in Sweden and assess possible risk
factors associated with the occurrence of adverse reactions to these agents.
METHODS: A survey was made of 1202 reports describing 1861 adverse reactions
to SSRIs submitted to the Swedish Adverse Drug Reactions Advisory Committee.
RESULTS: The most often reported adverse reactions were neurological symptoms
(22.4%), psychiatric symptoms (19.5%) and gastrointestinal symptoms (18.0%);
however, dermatological symptoms (11.4%) and general symptoms (9.8%) were also
frequent. Compared with other drugs, gastrointestinal symptoms were more often
reported for fluvoxamine, psychiatric symptoms were more often reported for
sertraline and dermatological symptoms were more often reported for fluoxetine. In
total, the diagnoses most frequently reported were nausea (n = 139), rash (n = 90),
anxiety (n = 84), paraesthesias (n = 69), headache (n = 63) and diarrhoea (n = 63).
Parkinsonism, confusion, hallucinations, euphoria, hyponatraemia, bradycardia and
hypotension were more often reported in the elderly, whereas urticaria, akathisia, and
haematological, endocrinological, sexual and some visual reactions were more often
reported in individuals who were younger than average. Dermatological reactions,
fatigue, hyponatraemia and cough were more common in women, whereas
dyskinesias/akathisia and aggression more often were seen in men. The median SSRI
dosages were above average in patients experiencing seizures, hypomania/mania,
personality changes, malaise, bodyweight gain, gynaecomastia and
hyperprolactinaemia/galactorrhoea. Severe symptoms, such as seizures, hyponatraemia
and the serotonin syndrome, were rarely reported. CONCLUSION: Although the
design of the study makes it difficult to draw conclusions about causality, a variety of
adverse reactions were reported. Therefore, the awareness that a particular symptom
in a patient treated with an SSRI might be an adverse reaction should be high.
 
 
 

TITLE:   SSRI-induced mania in obsessive-compulsive disorder
AUTHOR:  Diler-RS; Avci-A
JOURNAL:  Journal of the American Academy of Child and Adolescent Psychiatry; VOL 38, ISS 1, 1999, P6-7.
PY: 1999
LA: English
MIME: Case-Report; Child-; Female-; Human-; Male-
MJME: *Bipolar-Disorder-chemically-induced;
*Obsessive-Compulsive-Disorder-drug-therapy; *Paroxetine-adverse-effects;
*Serotonin-Uptake-Inhibitors-adverse-effects
PT: LETTER
RN: 0 (Serotonin Uptake Inhibitors); 61869-08-7 (Paroxetine)
ISSN: 0890-8567
CO: HG5
UD: 199904
AN: 99109286
 

TITLE:   Rational polypharmacy in the bipolar affective disorders.
AUTHOR:  Post-RM; Ketter-TA; Pazzaglia-PJ; Denicoff-K; George-MS; Callahan-A;
Leverich-G; Frye-M
Biological Psychiatry Branch, NIMH, Bethesda, MD 20892-1272, USA. 
JOURNAL: Epilepsy Res. Suppl.; VOL 11, 1996, P153-80 (REF: 105).
PY: 1996
LA: English
AB: Bipolar affective illness represents a syndrome not readily treated by single agents.
Approximately 50% of patients are inadequately responsive to lithium and the majority
of patients require supplemental antidepressants, antimanic, antipsychotic or hypnotic
medications. These traditional adjunctive medications are associated with potential
problems. Antidepressants may precipitate mania (at a rate about double that of placebo) or cause cycle acceleration. Neuroleptics may be associated with either more profound or longer depressive phases, and clearly increase the risk of tardive dyskinesia, to which bipolar patients appear particularly predisposed. Moreover, there are subgroups of patients who are known to be poorly responsive to lithium. These include patients with rapid cycling, dysphoric mania, co-morbid drug or alcohol abuse, a pattern of depression-mania-well interval (D-M-I as opposed to the M-D-I pattern), and patients without a family history of bipolar illness in first-degree relatives.

There is increasing recognition that the anticonvulsants carbamazepine and valproate are effective alternatives or adjuncts to lithium in the acute and long-term treatment of bipolar illness. Ideally, one would want to assess whether patients who were unresponsive to lithium were responsive to an anticonvulsant alone prior to utilizing lithium in addition to anticonvulsant combination therapy. However, from the clinical 
perspective, it is often more expedient to use an anticonvulsant adjunctively to lithium to assess the efficacy of this combination and establish mood stabilization. When lithium is not discontinued, the increased morbidity during lithium withdrawal also would not occur and would not confound the evaluation of the new agent. We suggest the initial use of acute adjuncts to lithium with the anticonvulsants carbamazepine or valproate (instead of neuroleptics) so that their efficacy can be assessed in the individual's acute episode, with the likelihood of a positive response in longer-term prophylaxis.

Hypnotic benzodiazepines with anticonvulsant properties, such as clonazepam or lorazepam, are often used to help to induce sleep in escalating bipolar patients, and may be useful adjuncts as well. Patients who were inadequately responsive to either carbamazepine or valproate alone may be responsive to the anticonvulsant combination. In a similar fashion, one can also utilize several mood-stabilizing drugs (lithium and an anticonvulsant such as carbamazepine or valproate) in the treatment of depressive breakthroughs, and then augment this combination (if necessary) with a catecholamine-active antidepressant such as bupropion or a serotonin-selective reuptake inhibitor (SSRI) such as fluoxetine, paroxetine, sertraline or if necessary a monoamine oxidase inhibitor (MAOI). Once the patient has responded to a combination of drugs, it becomes problematic to decide whether the last agent added was the crucial ingredient in helping the patient achieve remission or that remission might have occurred with this agent alone. A conservative approach would have merit in patients who are finally stabilized on complex polypharmacy regimens only after many years of sequential trials; in this instance, the potential risk of re-exacerbating the illness with a taper of one of the drugs in the regimen. Rational polypharmacy should thus be implemented with careful delineation of the prior course of illness (typically using life chart methodology) and targeted treatment outcomes titrated against side effects, using sequential clinical trials in individual patients who have not adequately responded to monotherapy. In this fashion, it is hoped that pharmacodynamic differences among agents can be maximized and pharmacokinetic and side effects minimized.