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Guest Editorial
Highlighting Bipolar II Disorder
Gordon Parker, MD, PhD, DSc, FRANZCP
(PDF)

In Review
Neurobiological Findings in Bipolar II Disorder Compared With Findings in Bipolar I Disorder
Brent M McGrath, BSc, MSc, Phillip H Wessels, MD, FRCPC, Emily C Bell, BSc, MSc, Michele Ulrich, BSc, Peter H Silverstone, MB, BS, MD, MRCPsych, FRCPC
(PDF)

Bipolar II Disorder: An Overview of Recent Developments
George Hadjipavlou, MA, MD, Hiram Mok, MA, MB, BCh, BAO, FRCPC, Lakshmi N Yatham, MBBS, MRCPsych, FRCPC3 (PDF)

Review Paper
Bipolar Disorder: It’s All in Your Mind? The Neuropsychological Profile of a Biological Disorder
Gin S Malhi, BSc, MB, ChB, MRCPsych, FRANZCP, Belinda Ivanovski, Ssc Psychol, M Clin Psychol, Viktoria Szekeres, BSc,Psychol
(PDF)

Original Research
Impact of Culture on Depressive Symptoms of Elderly Chinese Immigrants
Glenda MacQueen, MD, PhD, FRCPC
Daniel WL Lai, PhD
(PDF)

Development and Reliability of a Pictorial Mental Disorders Screen for Young Adolescents
Nicole Smolla, PhD, Jean-Pierre Valla, MD, MSc, Lise Bergeron, PhD, Claude Berthiaume, MSc, Marie St-Georges, MPs
(PDF)

Command Hallucinations Among Asian Patients With Schizophrenia
Theresa MY Lee, MBBS, MMed, Siow Ann Chong, MBBS, MMed, Yiong Huat Chan, PhD, Gangaharan Sathyadevan, MBBS, MRCPsych
(PDF)

The Centre for Addiction and Mental Health Concurrent Disorders Screener
Juan C Negrete, MD, FRCPC, Jane Collins, MSc, Nigel E Turner, PhD, Wayne Skinner, MSW
(PDF)

Validation de la version française du questionnaire de Sociotropie-Autonomie de Beck et collègues
Mathilde M Husky, MSc, Olivier S Grondin, MSc, Philippe D Compagnone, PhD
(PDF)

Brief Communication
Depressive Symptoms and Alcohol Consumption Among Nonalcoholic Depression Patients Treated With Desipramine
Benjamin I Goldstein, MD, PhD, Ayal Schaffer, MD, FRCPC, Anthony Levitt, MD, FRCPC, Ari Zaretsky, MD, FRCPC, Russell T Joffe, MD, FRCPC, Virginia Wesson, MD, R Michael Bagby, PhD
Pierre Bleau, MD, FRCPC
(PDF)

Letters to the Editor
(PDF)

Safety of Clozapine in 2 Successive Pregnancies

Revisiting the Diagnostic Challenges of Secondary Mania and Bipolar Disorder in a Patient With Borderline Hyperthyroidism

Dyslipidaemia and Psychiatric Patients

Dream Contents in Patients With Major Depressive Disorder

Sensory Deprivation and Disorders of Perception

Re: The Internet’s Impact on the Practice of Psychiatry

Response: The Internet’s Impact on the Practice of Psychiatry

Denial and Avoidance in an Unusual Case of Death From Breast Cancer

Interferon-Induced Mania

Drug-Induced Psychosis After Long-Term Treatment With Levetiracetam

Priapism

An Ounce of Prevention: “COPEing with Toddler Behaviour”

Internet Gaming Addiction

Letters to the Editor

Safety of Clozapine in 2 Successive Pregnancies

Dear Editor:
With the introduction of atypical antipsychotics, it was predicted that the incidence of hyperprolactinemia-induced infertility problems would decrease. However, the use of atypical antipsychotics during pregnancy is an area with more questions than answers. We present a case wherein clozapine therapy was continued successfully over 2 consecutive pregnancies.

Case Report

MK, aged 25 years and a housewife of rural background, was premorbidly well adjusted, with a family history of depression. She had an acute-onset 7-year continuous illness precipitated by the death of her father. The illness was characterized by auditory hallucinations (that is, commenting and commanding), tactile hallucinations, passivity phenomenon, aggression, negative symptoms, and disturbed biofunctions. There was no history suggestive of depression or mania, substance abuse, or head injury. During this period, treatment tolerance or resistance was seen with various antipsychotics (that is, chlorpromazine, haloperidol, trifluperazine, and risperidone). Hence, clozapine was initiated after baseline investigations up to 400 mg daily. With 8 months of treatment, significant improvement in psychopathology and functioning occurred, with associated weight gain of 10 kg. Over the next 3 years, clozapine was gradually reduced to 200 mg daily with no reemergence of positive symptoms but persistence of negative symptoms. MK was married in early 2001 and continued to take clozapine. She was informed about the risk of congenital malformations with antipsychotics and was advised to use contraception. However, she conceived after 6 months of marriage and continued with the pregnancy and with clozapine. Venereal Disease Research Laboratory Slide Test (VDRL), HIV, and hepatitis B surface antigen titers were negative during the first trimester, and there was no evidence of congenital malformations during antenatal ultra- sonography on repeat occasions. Hemoglobin was 9.6 gram percent at the 10th week of pregnancy; folic acid and iron supplements were initiated at 10 and 16 weeks, respectively. Pregnancy-induced hypertension (PIH) was detected at the 38th week and was monitored. At the beginning of the 39th week, a 3-kg boy was delivered by episiotomy, with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. The postnatal period was uneventful, with normal developmental growth until age 20 months.

Eight months after the first delivery, the patient reconceived and continued the pregnancy while on clozapine 100 mg daily. PIH occurred at 30 weeks and was managed with methyldopate hydrochloride 1500 mg daily. At 39 weeks, a 2.8-kg girl in breech presentation was delivered by elective cesarean section. The baby’s Apgar scores were 7 and 9 at 1 and 5 minutes, respectively, with no postnatal complications. Developmental status was normal until age 6 months.

Discussion

Clozapine is a “Category B” drug with no controlled studies in pregnant women. Available data are generally in the form of case reports or series (1).

A recent review reported 5 congenital malformations and 5 perinatal syndromes in each of 61 children exposed to clozapine (1). Various associations with maternal exposure include floppy infant syndrome (2), neonatal seizures (3), new onset or worsening of gestational diabetes mellitus with shoulder dystocia (4,5), decreased variability of fetal heart rate (6), and intrauterine growth retardation with oligohydroamnios (7). However, use of drugs concomitant with malnutrition and family history of diabetes mellitus have been certain confounding factors.

Conversely, Waldman and others reported at least 15 normal births with maternal clozapine exposure and have discounted definite association between clozapine and congenital malformations (4).

In the case of our patient, clozapine was not associated with any adverse effects on the fetus (including congenital malformations) over 2 consecutive pregnancies, which adds to clozapine’s safety data and is in keeping with a recent suggestion that it may be justifiable to continue clozapine during pregnancy when benefits outweigh the risks (8).

References

1. Ernest CL, Goldberg JF. The reproductive safety profile of mood stabilizers, atypical antipsychotics, and broad spectrum psychotropics. J Clin Psychiatry 2002;63(Suppl 4):42–55.

2. DiMichele V, Ramenghi LA, Sabationo G. Clozapine and lorazepam administration in pregnancy [letter]. Eur Psychiatry 1996;11:214.

3. Stoner SC, Sommi RW Jr, Marken PA, Anya I, Vaughan J. Clozapine use in two full term pregnancies [letter]. J Clin Psychiatry 1997;58:364–5.

4. Waldman MD , Safferman AZ. Pregnancy and clozapine. Am J Psychiatry 1993;150:168–9.

5. Dickson RA, Hogg L. Pregnancy of a patient treated with clozapine. Psychiatr Serv 1998,49:1081–3.

6. Yogev Y, Ben-Haroush A, Kaplan B. Maternal clozapine treatment and decreased heart rate variability. Int J Gynecol Obstet 2002;79:259–60.

7. Mendhekar DN, Sharma JB, Srivastava PK, War L. Clozapine and pregnancy. J Clin Psychiatry 2003;64:850.

8. Nguyen HN, Lalonde P. Clozapine and pregnancy. Encephale 2003;29:119–24.

Nitin Gupta, MD,
Staffordshire, UK;
Sandeep Grover, MD,
Chandigarh, India