Patient perspectives of lithium and quetiapine augmentation treatment in treatment-resistant depression: A qualitative assessment

Apprehension towards lithium

Prior to initiation, nine participants (six of whom had been subsequently randomised to quetiapine and three to lithium) held beliefs that lithium might be a more ‘extreme’ treatment than quetiapine. Reasons for expressed apprehension differed. For some, awareness of the necessity for blood tests to ensure lithium levels remained in the therapeutic range and the possibility of lithium toxicity resulted in greater apprehension at the prospect of taking lithium compared to quetiapine:

P: It seemed the more extreme of the two options, erm . . . was hoping that I wouldn’t be randomised to that one but I was . . . just in terms of like the blood tests and the monitoring . . . (P23)

Other concerns were generated from reading the information sheet about lithium prior to treatment. Some described feeling worried about specific side effects listed:

P: Reading about the two, the quetiapine seemed like the less scary option. (P23)

P: I read about them and I um I thought that um lithium seemed like it would be harder on the digestive system than quetiapine might. (P14)

Some felt apprehensive following their own research prior to the study:

P: I think like stuff that you read it isn’t really science based, I think it’s a bit scary if you don’t . . . until you understand actually it’s just another, another treatment. (P23)

Others simply held a negative preconception of lithium based on their feelings towards it before randomisation:

P: I had quite a negative feeling towards it – I don’t know maybe in my subconscious I felt it wasn’t didn’t feel – like something I wanted to take. (P19)

Worry about side effects

One-quarter of participants stressed concerns regarding the potential side effects of lithium and quetiapine treatment before the trial. For example, several felt concerned that sedation might compromise their daily life functioning and performance at work:

P: I was worrying if I was just going to be falling asleep at work. (P8)

Others were concerned at the potential for weight gain, which was listed as an adverse effect for both agents:

P: the main thing about whether or not I want to take part, and I went back for ages, was worrying about like the weight gain. (P2)

P: coz like I had an eating disorder like the weight thing was quite a big issue for me . . . I was just really really worried about that. (P2)

For some, the need to effectively treat their depression seemingly outweighed these concerns:

P: weight gain was obviously a concern, but I had to weigh up my mental health and, you know, a bit of weight gain. So you know, that was it. (P7)

P: I think I’ve got to the point where I’d tried 8 antidepressants and still felt awful so I was like, I’ll give it a go (laughs) it can’t – it can’t be worse than the side effects of anything else. (P16)

Side effects with quetiapine

Side effects with quetiapine were near universal. Generally, patient narratives indicated feelings of sedation and unwanted weight gain to be most troublesome.

For some, feelings of sedation were overbearing and were thought to negatively impact their treatment outcome:

P: side effects were just exhaustion and tired um almost comatose in the mornings. (P6)

P: it was horrible I would sort of wake up in the morning and still be like I hadn’t had a-a night’s sleep. (P6)

P: I was just completely wiped out all the time, I mean I was just zonked permanently basically so it wasn’t a feasible option to go forward basically. (P22)

However, two respondents felt sedation helped to improve their sleep which was previously disrupted:

P: it definitely helps so much with my sleep erm, because my sleep used to be really bad . . . whereas now like I know I take it and then like within half an hour I fall asleep. (P2)

Issues with unwanted weight gain and appetite increase were also among the most commonly reported side effects for quetiapine:

P: having a plan for um . . . for weight management is a good, is a good thing to do um . . . cuz that’s been, that’s been pretty difficult. (P14)

P: one thing that’s caught me out is the appetite that I just get big bursts of cravings of food. (P8)

The number of side effects reported differed, and for some, several different side effects were reported. Alongside sedation and weight gain, one participant perceived quetiapine to be worsening other pre-existing symptoms:

P: sleep and weight gain and I also like my um . . . the level of uh constipation and diarrhoea and how much that’s affect, been affecting me . . . it certainly hasn’t improved um it might have gotten worse since I started taking quetiapine. (P14)

Side effects with lithium

Patients receiving lithium generally indicated side effects to be more manageable. Despite this, several participants did report negative experiences.

Some described issues with tremor. Mostly, this appeared manageable and unproblematic:

P: Just a little bit of a shudder in the hands when I was trying to do something gently but that’s neither here nor there. (P27)

P: only issue that I’ve had that I think is actually related to the medication is err tremor that comes and goes but it’s mild and it doesn’t cause me any issues. (P18)

However, one subject described their tremor as severe, leading them to contact the study team for support:

P: Side effects were shakes, shakes you know, until I got shakes . . . I was trying to text you I think and then . . . Bad it was. (P3)

Several patients discussed issues relating to dry mouth. Despite being aware of the potential for dry mouth before treatment, one participant emphasised the disparity between their perception and the reality of experiencing it:

P: it’s one thing to hear someone say it and then to live through it um . . . it just literally is just a constant sort of dry mouth and not quite a constant thirst but you really have to discipline yourself to just keep drinking. (P13)

Vivid dreams were not listed as an adverse effect for lithium but were discussed by one participant:

P: The bad things were the dreams. They were basically making it a night reality . . . and certain dreams that you have can be quite frightening. (P26)

One participant discussed adverse effects on the kidney resulting in treatment discontinuation:

P: for me it would be the kidney side effects, you know. That’s what damaged me. (P25)

Managing side effects

Several subjects volunteered information about the action they took to better manage side effects.

Participants talked about the importance of the time they took their quetiapine medication each day:

P: we started taking it earlier and then it would help me sleep and it sort of got to manage that those side effects. (P6)

P: and also like play with what time of the evening is right to take the medication before you go to bed um . . . because that uh was definitely a balance to strike. (P14)

Several participants taking lithium described efforts to increase water consumption. One recognised that increasing their water intake could reduce the severity of their side effects:

P: I felt like some of the side effects got better because I was actually like staying hydrated and things. (P16)

For another, managing their weight gain enabled them to make positive changes:

P: being on the . . . quetiapine helps me, like I haven’t been – stepped inside a gym or swimming pool for like over seven years so, for me to go swimming and stuff is a – is a big thing so, it’s helping me um do that. (P7)

Improvement in symptoms

Six participants taking lithium described considerable improvements in their symptoms and mood:

P: I’ve come from down here, say naught, up to ninety-nine honestly, the amount of people that have said how different I am in this last year, and I’ve been down for years so this is great for me absolutely great. (P4)

Six participants taking quetiapine also reported large improvements, with some specifically mentioning changes in anxiety and panic symptoms:

P: the most major thing was not having all the anxiety and panic attacks because that strips away all the really good emotions that you feel . . . So um it’s been nothing but a godsend really. (P7)

Others described the key benefits of their treatment as better illness management and greater ability to cope within difficult circumstances:

P: there were times of the year as well as situations that usually would uhh would trigger depressive thoughts or sometimes even a depressive episode . . . I did have those difficult thoughts and you know a day where it was, when I was a bit down but it didn’t feel like depression, it didn’t feel like, it didn’t feel like hopelessness. (P14)

P: I would like to share the analogy of um . . . driving and being lost and it’s pointless carrying on driving and getting more lost if you can stop, get out the car and look at a map. Which is what the medication has helped me to do. (P8)

Mild and steady improvements

Some participants reported experiencing milder improvements in their symptoms.

One subject taking lithium reported this type of symptom change:

P: it was maybe two days out of the week that I felt a little better and five days I was still really, really low. From my point of view, I was going from zero positive days and so it was a benefit, it was a positive. (P22)

Others had difficulty delineating just how effective lithium was:

P: it’s kind of hard to tell, it’s not – I’m not exactly where I’d want to be um, but it’s . . . ok – it’s better than being where I was, so. (P17)

Some discussed the pace of improvement to be noticeably slow for lithium:

P: I can feel that there is something happening, but at a very slow pace though, but it doesn’t happen overnight. (P21)

Two patients did not perceive large improvements from taking quetiapine, but still felt it had been useful for them:

P: I think there was definitely a mild improvement. (P19)

P: no its uh – it’s been fine, it’s uh been worth trying. (P31)

Ineffective treatment(s)

Despite largely positive views of these medications, over one-quarter of participants did not perceive any benefits from treatment.

For some, the only noticeable change from taking quetiapine was the side effects:

P: I don’t notice a lot of change in myself um and that has been the case with all of my medications umm with the exception of the tiredness that is the only physical change that I have felt. (P6)

One participant did not perceive any improvement with dosages that corresponded with a safe lithium plasma level:

P: I just didn’t feel a . . . that much of a beneficial effect er until I was on a higher dose but then my blood levels showed that my lithium levels were too high so it had to go back down again. (P32)

Some participants reported self-blame for a lack of perceived symptom change. One participant treated with both medications described frustration at their failure to benefit from either one:

P: the fact that neither of them really worked . . . didn’t really dishearten me. I mean it . . . it’s frustrating from my personal point of view erm, that I feel like I’m rubbish basically you know it’s . . . it’s me. (P22)

Another who did not perceive benefits from lithium felt this could be due to their own expectations:

P: I think my personal problem was that I expected too much. (P29)

Some attributed failure to benefit as a consequence of difficult personal circumstances:

P: I’ve had such a difficult 12 months it’s then unfair in respect to the trial it’s been two deaths, a cancer scare and then 9 months off work through mental so it would be nice to have it on 12 months of normal. (P6)

A good number of appointments

Participants were generally positive about the number of clinical appointments they were required to attend:

P: I felt like I I . . . it was useful to have that many. (P14)

P: the frequency, if anything gave me more positivity. (P22)

P: the frequent appointments, although I had to take time off work to come to them, they were really useful. Um I felt like I was being looked after, um and that I wasn’t really on my own in it, um which I think is something I kind of felt for a long time. (P17)

However, some felt the number of appointments might prove difficult:

P: it took an amount of effort, so I guess yeah I guess a good way to put it is if someone is particularly, suffering particularly badly . . . with depression, that might be an extra challenge. (P13)

Reassurance from quick communication

There was a sense of reassurance among participants regarding the speed and ease of communication with both the study team and clinicians.

For some, this was particularly useful when side effects became problematic:

P: I got a bit stressed about weight and stuff so I wanted to go down to a lower dose and it was like good, they were really quick to like reply and like get me an appointment with the psychiatrist . . . so that was really useful. (P2)

P: it’s been amazing um. So (doctors name) sees me regularly um and I can email if there’s any concerns as well, which s/he replies within 24 hours. (P7)

P: it was good cos I could contact um the researcher or the psychiatrist and get if there’s any worries I could contact anybody and they would get back to me quickly. (P15)

‘Wasn’t as bad as I thought’ – blood tests were unproblematic

This subtheme refers specifically to patients treated with lithium which required clinical blood monitoring throughout treatment. Overall, patients showed a largely positive response to the required blood tests.

Some felt the blood tests were easier than they had initially perceived them to be:

P: it feels like quite a big undertaking with like the monitoring and the blood tests and stuff but it was fine, like it was easier than I . . . yeah it wasn’t a big, wasn’t a big problem at all. (P23)

P: I was first like startled by the amount of blood tests that I had to have, but I kind of got used to it so, apart from that it was absolutely fine. (P17)

Others described acceptance of the need for blood tests as a part of lithium treatment:

P: although you know, blood tests aren’t fun, it was good to have them because . . . you know it was, I needed to know what level it was in my blood um but yeah, overall I was happy with it. (P17)

P: They were definitely useful um obviously when there were more of them earlier on I had to sort of plan around them but I understand why it had to be like that. (P18)