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Adel Gabriel, MB, BCh, FRCPC, LMCC, DPM, DPIP, DTM&H;, and Galal Fahim, MB, BCh, LMCC

Primary Psychiatry. 2005;12(4):59-60

Focus Points

  • Clinicians should be aware of the comorbid psychiatric symptoms and disorders associated with major depressive disorder (MDD).
  • As demonstrated in the case study, the presentation of MDD is colored by different biopsychosocial factors in each patient.
  • Clinicians should be cautious when administering progesterone preparations or oral contraceptives with high doses of progesterone, especially in patients at high risk for MDD.
  • Recent evidence of the success of estrogen in treating MDD should be interpreted cautiously, and should stimulate further research in this area.

Abstract

This article presents a case study of major depressive disorder (MDD) and dissociative symptoms of retrograde amnesia following the administration of a depot medroxyprogesterone (DMP) contraceptive. A MEDLINE search stimulated by the case found very few studies and case reports to suggest that DMP can be followed by depressive symptoms. In some studies, weak evidence suggested that progesterone may even improve depressive symptoms in the postnatal period. There is also growing evidence to support the hypothesis that estrogen may improve depressive symptoms in postnatal and perimenopausal women. There is no literature to explore the effect of progesterone administration on memory in humans. Overall, there is contradicting evidence with regard to the effects of DMP on mood. Therefore, DMP should be used cautiously in high-risk patients. To date, hormones are not recommended for the treatment of postnatal MDD. Further studies are necessary to explore any possible casual relationship between DMP and mood disorders, and if that drug can result in memory deficits.

Introduction

This article presents a case of major depressive disorder (MDD) with prominent retrograde amnesia that lasted 6 months following the administration of a depot medroxyprogesterone (DMP) contraceptive. It also reviews the literature pertaining to the relationship between the administration of progesterone and mood changes or memory impairments. It proposes a link between DMP and depressive symptoms, although further research on this subject is required.

Case Presentation

Ms. X was a 22-year-old recently married female who held a job as a legal assistant, and had no past history of psychiatric disorders. Approximately 4 weeks prior to her marriage, she was administered a DMP contraceptive injection for the first time. At that time, she was on no other medications or contraceptives.

Following the injection she became progressively depressed, irritable, reported frequent crying spells, and voiced suicidal ideas. She had difficulty sleeping, poor appetite, and excessive anxiety. She was unable at concentrate at work, and her memory showed significant lapses in memory for recent events. She had difficulty in acquiring new information and reported vague auditory experiences. In fact, she presented with complete loss of all memories around the period of her marriage almost immediately following the ceremony, left the matrimonial home, and was in denial that she was married to her husband (who accompanied her to the consultation), identifying him as a friend. The husband and her family members were very understanding and supportive, though there were a number of stressful events that were associated with the marriage, as well as other occupational stresses.

Before treatment, Ms. X was unable to give a history, giving many “don’t know” answers to questions, was sluggish, and was slow in the interview. Her affect was indifferent, she looked rather expressionless and emotionless, and admitted to persecutory fears. Her memory was sketchy for many events from the recent past, and continued to suffer from retrograde amnesia for the period around her marriage.

This gradually improved through treatment over 6 months. Unfortunately, formal cognitive neuropsychological testing could not be completed due to her poor attendance. She had not been treated previously for any psychiatric symptoms, had no family history of psychiatric illness, no history of any drug or alcohol abuse, no history of head injuries or epilepsy, and no neurological deficits found on physical examination. Investigations, including complete blood count, electrolytes, computed tomography scan, and thyroid-stimulating hormone, were within normal limits. An electroencephalogram report was suggestive of pseudo-seizure.

Ms. X was treated with paroxetine 20 mg/day and supportive psychotherapy. This patient had suffered a first breakdown of MDD, with psychotic and dissociative symptoms. However, with treatment, mood symptoms and cognitive functions were recovered completely.

Both mood and memory difficulties in this patient can be explained not necessarily by the administration of DMP. Psychosocial stresses, including the ongoing occupational stressors, the significant life event of the recent marriage, and leaving the parental home (especially in a dependent personality), may have contributed to the causation of her symptoms. However, the role of DMP as a precipitating organic factor should be born in mind.

Discussion

There are few controlled studies with a sufficient number of patients to examine the link between DMP contraception and depressive symptoms or memory functions. In a recent large prospective study, Civic and colleagues1 compared 183 women who used the depot with 274 women who did not use DMP. The analysis of this study concluded that there was an association between DMP use and depressive symptoms, and that depressive symptoms subsided at subsequent visits relative to non-users.

In a survey, Westhoff and colleagues2 found that depression scores were somewhat higher among those women receiving their first DMP acetate injection during the study period and among those women who had received four or more injections. They concluded that the data provided little evidence of increasing depression with long-term use of DMP acetate and no evidence of a short-term effect of dose (within the contraceptive range) on mood. The authors suggested that women at risk for MDD should not be denied DMP acetate as a contraceptive choice.2

Westhoff3 and Westhoff and colleagues4 also summarized the existing literature regarding metabolic parameters and mood changes in women using DMP, and concluded that data regarding depression or mood changes in DMP acetate users are scant and do not support a causal relationship between the use of this contraceptive and affective disorders.

Granger and Underwood5 reviewed the literature from 1996–1999 and concluded that progesterone is being used to prevent recurrence of postnatal depression but the evidence supporting its efficacy is lacking. Its use in the treatment of postnatal mood disorders cannot be recommended on the basis of current evidence. Randomized controlled trials are needed to decide if it has a role in the treatment and prevention postnatal mood disorders.5

Lawrie and colleagues6 found that depot norethisterone enanthate given within 48 hours of delivery and lasting 8–12 weeks was associated with significantly higher postpartum depression scores than placebo. The authors suggested that norethisterone enanthate and other long-acting progestogen contraceptives should be used with caution in the postnatal period, especially in women with a history of depression.6 On the other hand, estrogen therapy has been reported to be superior to placebo in treating severely postnatal depressed women,7 and in a recent double-blind, randomized, placebo-controlled trial, Soares and colleagues8 demonstrated that transdermal estradiol replacement was effective in the treatment of depression in perimenopausal women.

A review of the literature indicates that few controlled studies have examined the association between the administration of DMP and the development of mood changes and amnesia, some of which are conflicting.1-3 Further research will be crucial to clarify the nature of this association.

Conclusion

It is premature to make the definite conclusion of a direct casual relationship between DMP and depressive symptoms at this time. This relationship may be crucial to establish in further research, since there are many individual variations in the response to hormones among women. Research is also required because of the many high-risk factors that may be associated with depression inpatients who receive DMP, such as age, length of exposure to the drug, the type and dose of the progestogen used, and family or individual history of psychiatric disorder.9 PP

References

1. Civic D, Scholes D, Ichikawa L, et al. Depressive symptoms in users and non-users of depot medroxyprogesterone acetate. Contraception. 2000;61(6):385-390.

2. Westhoff C, Wieland D, Tiezzi L. Depression in users of depo-medroxyprogesterone acetate. Contraception. 1995;51(6):351-354.

3. Westhoff C. Depot medroxyprogesterone acetate contraception. Metabolic parameters and mood changes. J Reprod Med. 1996;41(suppl 5):401-406.

4. Westhoff C, Truman C, Kalmuss D, et al. Depressive symptoms and Depo-Provera. Contraception. 1998;57(4):237-240.

5. Granger AC, Underwood MR. Review of the role of progesterone in the management of postnatal mood disorders. J Psychosom Obstet Gynaecol. 2001;22(1):49-55.

6. Lawrie TA, Herxheimer A, Dalton K. Oestrogens and progestogens for preventing and treating postnatal depression. Cochrane Database Syst Rev. 2000;(2):CD001690.

7. Galea LA, Wide JK, Barr AM. Estradiol alleviates depressive-like symptoms in a novel animal model of post-partum depression. Behav Brain Res. 2001;122(1):1-9.

8. Soares CN, Almeida OP, Joffe H, Cohen LS. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry. 2001;58(6):529-534.

9. Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR. Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry. 2000;157(6):924-930.

 


Dr. Gabriel is a consultant and clinical assistant professor of psychiatry and Dr. Fahim is an Alberta International Medical Graduate at the University of Calgary in Alberta, Canada.

Disclosure: Drs. Gabriel and Fahim report no affiliations with or financial interests in any commercial organization that might pose a conflict of interest.

Please direct all correspondence to: Adel Gabriel, MB, BCh, FRCPC, LMCC, DPM, DPIP, DTM&H, University of Calgary, 206, 2723—37th Ave NE, Calgary, Alberta, T1Y5R8 Canada; Tel: 403-291-9122; Fax: 403-250-3445; E-mail: gabriel@ucalgary.ca.