Perimenopausal depression

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Welcome to the Australian Prescriber Podcast. I'm Dr Ashlea Broomfield, your host for this episode, and it's a pleasure to be speaking to Jayshri Kilkarnii, the professor of Psychiatry at Monash University. Welcome.

Thank you very much.

So, Jayshri you have an article in this edition of Australian Prescriber on perimenopausal depression and what I noticed was really interesting about that was that the suicidal rates in perimenopausal women experiencing depression.

It is a severe form of depression and is accompanied by suicidal thinking and actually taking actions on that. There's been a rise in completed suicides in middle-aged women.

Certainly one of the most common presentations that I see in my general practice for this age group is significant mood changes. In your article you outline some differences between perimenopausal depression and other types of depression.

Yes, there can be a range of symptoms which include some of those that are seen in the more typical depression experienced by men or younger women. I think the differences in the perimenopausal depression are usually in quite a rapid and sudden onset that doesn't necessarily coincide with any particular new stresses in their work life or their family life or any other. And then with that sort of sudden onset there is often symptoms that accompany it like a really major shift in energy level. So that very pronounced loss of energy, along with that there can be paranoid thinking but it's not of a nature that would make one think about schizophrenia, it's more like the paranoia is expressed as everybody at work thinks I'm pathetic, I just can't learn new things, I think they're all talking about me behind my back. So, you can sort of understand that in a tense workplace there might be some friction but this becomes acerbated in the patient’s mind. Irritability or hostility is a really critical part of this and sometimes depression in the younger female or male patient may present more obviously with sadness, whereas here it could actually present as the woman being irritable and just losing her temper quickly in circumstances where she normally wouldn't. Decreased self-esteem. So sometimes we see in women in the middle 40s or a bit older presenting with very poor self-esteem and that seems to even take a greater nosedive at this time. Symptoms like sleep disturbance and appetite changes are of course seen in all kinds of depression but here again what seems to happen is a sudden onset change in sleep and so there can be fluctuations or cyclical patterns of this in the perimenopausal depression. So the common picture is someone will say I had you know sort of a week of just not sleeping very well, I was up every few hours and now I feel exhausted and then the following week it may settle down. Really reflective of the hormone shifts in the HPG or gonadal axis that are taking place that are impacting on her sleep. These particular hormone shifts are behaving very much in a fluctuating way and so that can account for all of the depression symptoms coming and going but when they come there's a ferocity and a severity that we should not ignore. Many, many women describe quite a rapid onset of a change in memory and that can be again quite dramatic and sometimes people do actually say I wonder if I’m developing Alzheimer's or some other dementia. Weight gain is common. This can take place especially the 2–3 kg weight gain even in the woman who has a very sensible diet and sensible exercise program. So again, the weight gain can of course contribute to worsening poor self-esteem. Sexual interest can change but again it's the fluctuation or sudden change in libido that we need to take note of.

You outlined in the article that often with the hormonal changes the mood symptoms pre-date the physical symptoms, yet we can consider whether hormonal therapy may be useful for the woman or not.

This is the really tricky part about this particular condition because transition to menopause changes begin about five years earlier in the CNS or brain rather than in the body. So once hot flashes occur then it's very obvious what is going on. The sudden change in functionality in a 45-year-old woman does alert us to the possibility that this is perimenopausal depression and in that situation the first step of hormone treatment is in fact to consider if she's still having cycles, the oral contraceptive pill, and we tend to use a combination pill that has oestradiol plus nomegestrol because it is a better progesterone for mental state. Some of the progesterones can be quite depressive themselves. Supportive psychotherapy for the woman is also critical. The use of antidepressants, it's a tricky one because SSRIs or SNRIs are associated with a number of side effects and in particular can include the exacerbation of weight gain, which is something that is already an issue for the perimenopausal woman. But nonetheless if suicidality is a big feature then of course we are going to make sure that we try to quickly and effectively deal with that symptom and this was probably where you use a combination of oestradiol therapy plus an SSRI.

Can we go back to when you talked about the particular type of oral contraceptive pill that you would use, and you described the oestradiol/nomegestrol pill as your first preference? My understanding is this is quite an expensive pill. What would be your second line that's a PBS listed pill?

The second-line, most commonly prescribed pill is 30 micrograms of oestradiol and levonorgestrel. Some of the pills that have particularly drospirenone as the progesterone component can actually create issues with both physical health and also irritability.

So, would you always use a combination in somebody who didn't have any contraindications to the oral contraceptive pill and was having suicidality?

I think the suicidality is the factor that denotes several things. One is dangerousness for the patient but also severity, and in that situation, I would be more keen to use a combination of hormone treatment and antidepressants.

Cause the hormone treatment we're assuming is not going to have any effect on the suicidality or it's so severe that they will need that little bit of serotonin to help?

They probably will need some serotonin but sometimes it's interesting the suicidality can be very complicated as well because if it's a lifetime story of chronic suicidal ideation but without action and there's a chronic suicide ideation related to early life traumas for example, then what we've also seen is in this population that flares up around the menopausal transition and all of a sudden the self-harm, deliberate self-harm behaviours exacerbate, and in that case it's very interesting that clinically that group of women do actually respond to oestradiol treatment because oestradiol in the CNS has so many different effects on the serotonin system itself as well as some of the GABA systems and some of the noradrenergic systems. So it's quite a potent neuroprotective agent and the hypothesis there is that estrogen has been this natural neuroprotection agent and then with declining levels menopause protection is diminished and hence some of the self-harm etc. behaviours become an issue again. So, it's certainly complex in terms of thinking about the suicidality but nonetheless it's a symptom that means that urgent and effective action needs to be taken.

Yeah, it definitely is a complex time in women's lives and as general practitioners we often are able to spend a fair amount of time with these women over a series of consults dealing with all the issues that can arise and so having that continuity in space and working out all these issues can be a really gratifying time. Do you have any specific resources for clinicians in order to read more about perimenopausal depression?

I have attached references. I would suggest that but again I'm really appreciative of being able to do this because it is about just getting this term out there that perimenopausal depression is a significant problem for middle-aged women and it's different to other depressions in terms of response and presentation.

So, the take-home message that I got from chatting to you was basically consider that perimenopausal depression has more of a biological, melancholic and severe type presentation particularly if it's abrupt and can have more of an irritability association with it. Consider the use of combined oral contraceptive pills in the younger women who don't have any contraindications and HRT in women that may be a bit older and a combination of SSRIs rather than continually switching in SSRIs and working in the psychotropic medication world, think about the biological side of the perimenopausal depression with hormones.

Yes, although I wouldn't use the word melancholic because that is the picture of the very sad person whereas it's very interesting this can be the angry woman, and nobody likes angry women, and so this is one of the reasons why the rapport is difficult with clinicians or getting help can be more difficult.

So unfortunately that's all the time we've got for this episode, thanks for joining us today.

Thank you.

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The views of the hosts and guests on the podcast are their own and may not represent Australian Prescriber or NPS MedicineWise. I'm Ashlea Broomfield and thanks for joining Jayshri Kulkarni on the Australian Prescriber Podcast.