Psychosomatics 49:163-167, March-April
doi: 10.1176/appi.psy.49.2.163
© 2008 Academy of Psychosomatic Medicine
Antipsychotic-Induced Hyperprolactinemia and Delusion of Pregnancy
Niraj Ahuja, M.B.B.S., M.D., M.R.C.Psych.,
Steve Moorhead, M.B.Ch.B., M.R.C.Psych.,
Adrian J. Lloyd, M.B.B.S., M.R.C.Psych., M.D., and
Andrew J. Cole, M.A., M.B.B.S., F.R.C.Psych.
Received June 12, 2007; accepted October 4, 2007. From the Northumberland, Tyne and Wear NHS Trust, and the School of Neurology, Neurobiology, and Psychiatry, University of Newcastle-upon-Tyne, UK. Send correspondence and reprint requests to Dr. Niraj Ahuja, Wallsend Community Mental Health Team, Sir G.B. Hunter Memorial Hospital, The Green, Wallsend, UK NE28 7PD. e-mail: niraj.ahuja{at}ntw.nhs.uk; Niraj.ahuja@ncl.ac.uk
© 2008 The Academy of Psychosomatic Medicine
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ABSTRACT
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The authors describe 12 patients with antipsychotic-induced hyperprolactinemia. Six patients had erroneous ideas of being pregnant (four delusional and two non-delusional) temporally associated with hyperprolactinemia and resolving as prolactin levels returned to normal. The remaining six patients did not develop such ideas. Contrasting the clinical features of the two groups of patients in the context of existing literature informs on the possible biological and cognitive mechanisms that can be hypothesized to underlie the relationship between hyperprolactinemia due to antipsychotics and the development of inaccurate beliefs and feelings about pregnancy, and the effect of current mental state on the propensity to develop these beliefs.
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INTRODUCTION
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Dopamine-blockade, associated with many antipsychotic drugs, is a well-recognized cause of hyperprolactinemia and extrapyramidal symptoms. The advent of atypical or second-generation antipsychotics (SGAs) brought optimism that they would not produce the range of adverse effects associated with typical, or first-generation, antipsychotics (FGAs), particularly extrapyramidal side effects (EPSE) and hyperprolactinemia. However, some SGAs (e.g., risperidone, amisulpride), can, in fact, cause increased serum prolactin levels, indicating that SGAs are not a group of medications with homogeneous "atypical" properties.
Prolactin secretion by the anterior pituitary is under the tonic inhibition of hypothalamic dopamine. Antipsychotic-induced hyperprolactinemia is due primarily to dopamine D2-receptor blockade, although serotonin (5-HT2) agonism has also been implicated. The common manifestations of hyperprolactinemia in women include amenorrhea and galactorrhea.
We have previously reported on a woman who presented with a delusion of twin pregnancy1 while she was experiencing mania with psychotic symptoms, the onset of which was temporally correlated with antipsychotic-induced hyperprolactinemia. A fall in serum prolactin, associated with modification of her antipsychotic medication, led to the disappearance of the delusion of pregnancy.
We now report four cases of delusion of pregnancy and two cases of non-delusional ideas of pregnancy associated with antipsychotic-induced elevations of serum prolactin. We contrast these cases with six other cases where the antipsychotic-induced hyperprolactinemia was not associated with similar delusions or ideas. We briefly review the literature and speculate on the possible mechanisms of a relationship between antipsychotic-induced hyperprolactinemia and the delusion of pregnancy.
Delusion of pregnancy can be described as a false and fixed belief about being pregnant, despite factual evidence to the contrary. Although it is believed to be a relatively rare symptom, it has been reported in both men and women. Delusion of pregnancy appears to be a nonspecific psychotic symptom that can occur in several disorders, including schizophrenia, schizoaffective disorder, delusional disorder, depressive disorder, mania, and dementia.1
The origin of the delusion of pregnancy has often been explained by psychological mechanisms, even when present in the setting of schizophrenia. However, organic factors have also been put forward as possible causes for delusions of pregnancy, particularly in men.2
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Case Report
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We report on 12 women who presented during the last year with antipsychotic-induced hyperprolactinemia. Six described an idea of being pregnant that was temporally associated with the hyperprolactinemia. These ideas were demonstrably delusional in four patients and non-delusional in two patients. The key clinical features of these patients are summarized in Table 1.
The four women ("Ms. A," "Ms. B," "Ms. C," and "Ms. D") who presented with delusions of pregnancy were all experiencing psychotic symptoms; two of them suffering from severe mania with psychotic symptoms, one with schizophrenia, and another with an acute relapse of psychotic symptoms in schizoaffective disorder. On the other hand, the women presenting only with ideas of "feeling pregnant" ("Ms. E" and "Ms. F") were both in clinical remission; one in a euthymic phase of bipolar disorder, and the other in remission from schizoaffective disorder. Of the six women without ideas or delusions of pregnancy ("Ms. G," "Ms. H," "Ms. I," "Ms. J," "Ms. K," and "Ms. L"), only one ("Ms. L") suffered from current psychotic symptoms. Despite being currently in a psychotic state, she had no anticipation of becoming pregnant and was not experiencing symptoms that were akin to her previous experience of pregnancy.
It is interesting to note that all six women with ideas or delusions of pregnancy also reported "feeling" pregnant on questioning. They described this as the feeling of abdominal distension and a "visceral" sensation of feeling pregnant. Only four of the six ("Ms. A," "Ms. B," "Ms. E," and "Ms. F") had a history of past experience of pregnancy and likened their current experience to the feeling of pregnancy in the past. Interestingly, none of our patients reported galactorrhea as a symptom of hyperprolactinemia. Of the patients with delusions of pregnancy, one was postmenopausal ("Ms. C"), and two had become amenorrheic ("Ms. B" and "Ms. D"). Both patients ("Ms. E" and "Ms. F") with non-delusional ideas of pregnancy had developed amenorrhea.
"Ms. C" was in a currently active heterosexual relationship although she had never been pregnant in the past. Despite being postmenopausal for several years, she "wanted" to get pregnant and readily interpreted any bodily sensations as evidence of pregnancy. She discounted menopause as a stumbling block to becoming pregnant.
"Ms. D" had never been pregnant or married, although she had become strongly infatuated with a man before the manic episode and "wanted" to become pregnant by him. The delusions of pregnancy, however, became apparent only 1 week after initiation of antipsychotic medication (Risperidone) in the hospital, and this correlated with documented elevated serum prolactin.
In all six patients, the ideas/delusions of pregnancy promptly disappeared soon after a change in antipsychotic medication to agents less likely to cause hyperprolactinemia. Reversion to normal prolactin levels was confirmed in five cases (within 1 week of normalization of serum prolactin. The return to normal of serum prolactin could not be confirmed in "Ms. B" because a blood sample had not been obtained. In three out of four patients, disappearance of the delusion of pregnancy occurred even before an improvement in other psychotic symptoms, whereas, in one patient, both the delusion of pregnancy and the other psychotic symptoms resolved together.
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Discussion
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In our patients, the delusion of pregnancy appeared in the midst of manic and/or psychotic symptoms. Although two of the women with delusions of pregnancy ("Ms. A" and "Ms. D") presented with manic symptoms, there was no manic flavor to the delusion of pregnancy itself in these cases. They did not ascribe any special significance to the pregnancy, nor did they allude to any grandiose ideation in relation to it.
The temporal association between antipsychotic-induced hyperprolactinemia and ideas/delusions of pregnancy was clinically striking in all six cases. We did not re-challenge any of our six patients with antipsychotics known to elevate prolactin; neither the patients nor the clinicians felt it to be clinically or ethically appropriate. We have previously reviewed the relevant literature to examine this hypothetical relationship1 and expand further on this association in light of the additional observations made in the patients reported here.
The presence of delusions of pregnancy with elevated prolactin is particularly remarkable, given that there is usually an inverse relationship between prolactin and psychotic symptoms. This seems reasonable because the degree of psychosis is often directly related to dopaminergic activity.
The cases described here add to previous similar reports in the literature3 of an association between delusions of pregnancy and biochemically-confirmed hyperprolactinemia due to antipsychotic medication. In all of these individuals, discontinuation of the offending antipsychotic led to fall in serum prolactin, with disappearance of the delusion.
Delusions of pregnancy are also reported in association with increased prolactin secondary to causes other than antipsychotics, for example, prolactinomas.4 One such case of organic delusional syndrome induced by hyperprolactinemia5 was successfully treated with the antipsychotic Melperone, which improved psychosis with minimal effect on prolactin level. Other reports of delusion of pregnancy associated with antipsychotic-induced galactorrhea6–8 are strongly suggestive of an association with elevated prolactin, although this was not confirmed biochemically in those patients One of these cases8 demonstrated a complete resolution of delusion of pregnancy after stopping depot antipsychotic medication, even though delusions of persecution were still present; this is consistent with our observations in three of our own patients.
It is of interest to note that prolactin has been suggested as playing a central role in the genesis of the "common" problem of pseudocyesis in domestic female dogs,9 and pseudopregnancy behavior is observed in a number of species.1
Although pseudocyesis and delusion of pregnancy have been reported as two independent phenomena, there appears to be considerable overlap between them.10,11 Some authors have described classical pseudocyesis as a neurotic or hysterical symptom, whereas delusion of pregnancy has been largely been seen as a psychotic symptom. Pseudocyesis presents with abdominal and breast enlargement, lactation, amenorrhea, description of fetal movements, and belief of pregnancy, although not all symptoms and signs are present in every patient. Delusion of pregnancy, on the other hand, is supposed to present only with false belief of pregnancy in the absence of physical signs suggestive of pregnancy. This phenomenon has been discussed in detail in our previous report.1 As stated above, all of our patients with ideas/delusions of pregnancy showed some degree of abdominal enlargement, amenorrhea (except in the case of "Ms. A"), and "feeling pregnant."
It is highly doubtful that delusion of pregnancy can be explained by a single etiological factor.7 Antipsychotic-induced hyperprolactinemia is clearly not likely to explain delusions of pregnancy in all patients. Long-standing delusions of pregnancy, although previously described,7 are uncommon, and, more often, these constitute a short phase in a more chronic presentation of psychiatric symptoms,1,8 as was the case in our patients.
Cognitive theory hypothesizes that delusions arise from normal cognitive processes directed at explaining abnormal perceptual experiences12 influenced by premorbid values and beliefs and in the context of information-processing vulnerabilities. The Interacting Cognitive Subsystems framework13 has helped to recognize the role of body-state information in influencing emotional states. This includes muscle memory and the idiosyncratic meaning of the enteroceptor information that informs and elaborates the emotional experience. This forms an important part of current understanding of the increasing vulnerability to relapse reported with increasing depressive episodes. Thus, body-state information that resembles a previous or anticipated (and emotionally-laden) experience will be a powerful activator of emotions and cognitive products. In vulnerability to depression, for example, it may reflect the experience of tiredness associated with the meaning of being depressed. Evaluation of the symptoms of tiredness would produce anxiety: ("I’m getting depressed again.") and depression: ("There’s nothing I can do to stop it ... I’m so useless.") In this case series, the production by prolactin of gross and subtle symptoms of pregnancy may activate memories of that state and associated thoughts and emotions about it.
A similar effect could be produced by physical-state experiences in someone who is cued to be vigilant for these experiences, for example, someone who desires to be pregnant (as reported here) or is dreading the idea of pregnancy. Prolactin might subtly but directly influence emotion, and there are likely to be other routes to such vigilance or to considering pregnancy as a possible explanation for physical experience.
The information-processing vulnerabilities recognized among those with delusional beliefs include a tendency to use less information and be more rapid when coming to a conclusion, to be more certain of the conclusion, and to be less likely to review the decision.14 These processes are likely to be exaggerated in emotionally salient events or situations. In particular, when individuals experience emotional arousal, the search for a meaning that is personally relevant is much stronger. Thus, in the context of being cued to be vigilant for symptoms of pregnancy, a small amount of enteroceptor signal that is perceived to be in keeping with pregnancy may result in disproportionate emotional arousal, and a feedback loop may be established that keeps attention focused on these symptoms, resulting in an increasingly firm belief in the pregnancy.
Therefore, in Patients A, B, C, D, E, and F, the reduction in serum prolactin, after discontinuation of antipsychotic medication, is likely to have been associated with a reduction in the stream of body-state information in keeping with pregnancy being received by the emotional-processing system, allowing the belief in being pregnant to decay.
In Patients G, H, and J, the absence of cuing (previous experience or emotional salience of the idea of being pregnant) that is relevant to pregnancy makes it much less likely that this is considered as an explanation for the experienced physical symptoms.
In Patients E and F, there is a clear history of experiencing enteroceptor information that is in keeping with pregnancy, but they did not draw the conclusion that they were pregnant. Rather, they both reported having dismissed the idea, even though "Ms. E" was anticipating pregnancy, and the symptoms would thus have emotional salience. Their ability to reflect on the idea and dismiss it may represent a response they were able to produce in a state of lower emotional arousal: both of them were in clinical remission and were not experiencing other psychotic or affective symptoms.
Recent therapeutic developments in cognitive-behavioral therapy (CBT) have focused on enabling people to do precisely what both these patients describe as their response to the thought: identifying it, considering it, and dismissing it. For some people, this requires some work on their beliefs about intrusive thoughts (such as "people should follow their feelings" or "my feelings are likely to indicate a greater truth than cold fact"); for others, this requires practice at accepting thoughts that intrude into their minds as mere "thoughts," without responding to them—such as trying to suppress them (resulting in rebound intrusion) or believe them as facts (resulting in behavior that maintains attention on the thought and emotional arousal).
Both Patients C and D demonstrate an alternative route to the salience of such intrusive ideas. They both report symptoms of pregnancy associated with hyperprolactinemia in the context of anticipated and desired pregnancy. Although such an explanation may be a post-hoc rationalization on their part, it is feasible within this model and would produce positive emotional arousal and vigilance for the symptoms. This could produce a maintaining cycle of enteroceptive sensation, evaluation of this as being pregnancy-related, emotional arousal, and conviction in the context of the described processing vulnerability.
The absence of pregnancy-related cognitions in Patient L suggests an important role for a cuing emotional salience of pregnancy (she did not anticipate or desire pregnancy, and she was postmenopausal) in addition to the experience of physical symptoms in keeping with pregnancy (she had been pregnant, and her hyperprolactinemia did not produce similar symptoms). Thus, in the context of active psychosis, her hyperprolactinemia was not associated with ideas or delusions of pregnancy without these two factors.
Clinical Implications
As illustrated by these 12 patients described with antipsychotic-induced hyperprolactinemia, half of whom presented with ideas/delusions of pregnancy, it is possible to generate biological and cognitive hypotheses as to the possible relationship between elevated prolactin and a specific abnormality in thought content (ideas of pregnancy) in psychotic states.
A more systematic study of serum prolactin and delusion of pregnancy would help clarify the link between the two, and, pending this, it would seem heuristically useful to inquire about symptoms of pregnancy and measure serum prolactin when investigating patients presenting with ideas/delusions of pregnancy. If hyperprolactinemia is found to be coexistent with delusion of pregnancy, a prolactin-sparing antipsychotic would be a better choice for treatment. It would be interesting to see whether the ideas/delusions of pregnancy are susceptible to CBT even if serum prolactin levels remain high. Such an approach would involve an inquiry about the presence of symptoms of pregnancy, education about the potential effects of the medication, and a collaborative approach to examining the evidence.
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ACKNOWLEDGMENTS
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Dr. Ahuja has received honoraria for lectures/travel grants from AstraZeneca, Bristol-Meyer-Squibb, Eli Lilly, Boehringer-Ingelheim, Janssen-Cilag, and Wyeth. Dr. Lloyd has received financial support (including travel funding) for academic work from AstraZeneca, Bristol-Meyer-Squibb, Eli Lilly, Janssen-Cilag, and Wyeth.
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REFERENCES
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- Ahuja N, Vasudev K, Lloyd AJ: Hyperprolactinemia and delusion of pregnancy. Psychopathology 2008; 41:65–68[CrossRef][Medline]
- Chaturvedi SK: Delusions of pregnancy in men: case report and review of the literature. Br J Psychiatry 1989; 154:716–718[Abstract/Free Full Text]
- Ali JA, Desai KD, Ali LJ: Delusions of pregnancy associated with increased prolactin concentrations produced by antipsychotic treatment. Int J Neuropsychopharmacol 2003; 6:111–115[CrossRef][Medline]
- Takeda M, Tanino S, Nishinuma K, et al: A case of hypophyseal prolactinoma with treatable delusions of dermatozoiasis. Acta Psychiatr Scand 1985; 72:470–475[CrossRef][Medline]
- Soygur H, Palaoglu O, Altinors N, et al: Melperone treatment in an organic delusional syndrome induced by hyperprolactinemia: a case report. Eur Neuropsychopharmacol 1997; 7:161–163[CrossRef][Medline]
- Shiwach RS, Dudley AF: Delusional pregnancy with polydipsia: a case report. J Psychosom Res 1997; 42:477–480[CrossRef][Medline]
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- Bitton G, Thibaut F, Lefevre-Lesage I: Delusions of pregnancy in a man. Am J Psychiatry 1991; 148:811–812[Free Full Text]
- Gobello C, de la Sota RL, Goya RG: A review of canine pseudocyesis. Reprod Domest Anim 2001; 36:283–288[CrossRef][Medline]
- Michael A, Joseph J, Pallen A: Delusions of pregnancy. Br J Psychiatry 1994; 164:244–246[Abstract/Free Full Text]
- Reichenbacher T, Yates A: Pseudocyesis as the presenting symptom in an adolescent patient with an incipient thought disorder. J Adolesc Health Care 1987; 8:456–459[CrossRef][Medline]
- Chadwick PO, Lowe CF: A cognitive approach to measuring and modifying delusions. Behav Res Ther 1993; 32:355–367
- Teasdale JD: Emotional processing, three modes of mind, and the prevention of relapse in depression. Behav Res Ther 1999; 37(suppl 1):S53-S77
- Garety PA, Hemsley DR: Delusions: Investigations Into the Psychology of Delusional Reasoning. Hove, Psychology Press Maudsley Monographs, 1994
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ABSTRACT
INTRODUCTION
