Parental experiences in the use of fluoxetine for management of ‘disruptive behaviours’ in children and youth with autism and pathological demand avoidance – a mixed methods exploratory study (Fluoxetine study)

doi:10.21203/rs.3.rs-4079890/v1

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Research Article

Parental experiences in the use of fluoxetine for management of ‘disruptive behaviours’ in children and youth with autism and pathological demand avoidance – a mixed methods exploratory study (Fluoxetine study)

https://doi.org/10.21203/rs.3.rs-4079890/v1

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Background

Pathological demand avoidance (PDA) is a relatively new profile described in autism spectrum disorder (ASD), characterised by an extreme resistance to everyday demands and social interactions and may present as aggressive, destructive behaviours. This study aims to explore (through use of parental recall) the utility of fluoxetine in managing disruptive behaviours attributed to PDA.

Methods

Mixed-methods study incorporating surveys and semi-structured interviews with caregivers.

Results

Extreme Demand Avoidance 8-item measure (EDA-8) survey results showed a significant decrease in most behaviours attributed to PDA, including a decrease in frequency of the child obsessively resisting and avoiding ordinary demands and requests and having difficulties complying with demands unless they were carefully presented. The majority of participants in this study indicated that their child had either a co-occurring diagnosis of an anxiety disorder or that their child experienced anxiety. After initiating fluoxetine, parents noted improvement in their child’s behaviours and consequently improvement in their family’s quality of life.

Conclusion

Fluoxetine shows promise as an effective treatment in improving disruptive behaviours in children with PDA. Given the high prevalence of anxiety in children with PDA, we propose that the disruptive behaviours of PDA are secondary to an embodied experience of anxiety in children with autism.

PDA

pathological demand avoidance

autism

fluoxetine

SSRI

disruptive behaviour

anxiety

Pathological demand avoidance (PDA) is a relatively new profile described in autism spectrum disorder (ASD), characterised by an extreme resistance to everyday demands and social interactions [1]. In addition to shared features with autism including persistent difficulties with social interaction and emotional regulation, two of the defining features of PDA are intense anxiety and aggressive, destructive behaviours. Individuals with PDA often exhibit an exceptional need for control over their environment and a preference for maintaining their own agendas, leading to a range of challenging behaviours [2]. These behaviours can include verbal and physical resistance, defiance, manipulation, and avoidance tactics, all of which can make daily routines and social interactions particularly challenging for both individuals with PDA and those around them [3]. These occur in response to ordinary requests, demands or expectations, and result in avoidance. People with PDA may not engage in typical, everyday activities such as getting ready to go to the park, going to school, or brushing their teeth. Newson et al. (2003) determined that in children with PDA, demands are not avoided because the activity is aversive but because the demand elicits anxiety [4]. Being asked an ordinary demand, such as to put away a video game, may trigger an anxiety response that varies from procrastination, to taking control and giving direction to others, to panic responses such as running away, shutdown, aggression, or self-harm [4]. While many children exhibit a need for control and autonomy, the responses seen in a child with PDA is perceived by others as a challenge to authority and rules categorized as disruptive behaviour.

PDA - the diagnostic dilemma

Pathological demand avoidance is not a distinct diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or the International Classification of Diseases (ICD-11). Rather, PDA is considered a behaviour profile within ASD that presents with unique features and challenges [5] (see Table 1). Similar symptoms in the autism spectrum have been reported in the literature, such as irritability and aggression (IA) [6]. The distinguishing aspect of the PDA profile lies in the notion that the behaviours do not involve choice. Individuals are unable to comply with requests, rather than deliberately choosing not to do so (‘can't’ versus ‘won't’). While aggression, elopement, self-harm, and selective mutism are seen in ASD, viewed through a PDA lens is that the autistic brain is overwhelmed by the demand [7, 8]. Further research and literature are needed to gain a deeper understanding of the specific factors that contribute to this distinct presentation.

Table 1

Key features of a PDA profile, adapted from the PDA Society
Feature	Example
a. Resists and avoids the ordinary demands of life	Avoiding the demand of putting shoes on to go to the park, even though this is an activity they enjoy
b. Uses social strategies as part of the avoidance	Giving excuses such as ‘my legs don’t work’
c. Appears sociable on the surface, but lacking depth in understanding	May have good verbal fluency, appear charming, or mimic social interactions, but play with peers may be rigid with a need to control or dominate play.
d. Experiences excessive mood swings and impulsivity	May have meltdowns and become triggered into a fight or flight response, often associated with high levels of anxiety
e. ‘Obsessive’ behaviour, often focused on other people	Can become obsessive about people which can lead to extreme clinginess and controlling behaviour
f. Appears comfortable in role play and pretend, sometimes to an extreme extent (this feature is not always present)	May pretend as living as another person or as an animal for prolonged periods of time

Given the debilitating impact of PDA on families’ quality of life and ability to function, finding options for management is imperative. Children with PDA rarely respond well to approaches that are typically effective in ASD, such as employing structure, routine, and behavioural reward principles [1, 9]. Despite the reduced effectiveness of non-pharmacological therapies, we could not identify any guidelines or clinical trials for pharmacologic management of PDA. Subsequently, the pharmacologic management is derived from treatment of IA or disruptive behaviours. Risperidone and aripiprazole are antipsychotic medications that have been studied in IA but have significant adverse effects, including weight gain, sedation, and metabolic changes [6, 10].

One of the authors is a paediatrician in a community-based clinic that sees a majority of neurodivergent patients and has been using the anxiolytic/antidepressant selective serotonin reuptake inhibitor (SSRI) fluoxetine to help address functional impairments associated with PDA. This study was conducted to determine whether the anecdotal improvement seen with use of fluoxetine on function in children (and subsequently the family’s quality of life) with a PDA profile is valid (a practice to evidence approach). This can lend a start to reformulating behaviours seen in PDA as a profound manifestation of an underlying, functionally-impairing anxiety as opposed to a new distinct subtype of autism. Lucchelli et al., (2018) found that fluoxetine can decrease self-injurious behaviours, ADHD-like symptoms and irritability at low doses in children with autism, but no studies have been conducted yet on the use of fluoxetine for PDA [11]. This study aims to contribute to the understanding of PDA in autism and begin to build evidence for treatment with SSRI’s as we hypothesize that PDA is likely a physical manifestation of anxiety.

Participants

Potential participants were identified via interrogation of the electronic record from AR’s community-based paediatric clinic. Participants were recruited through email and phone if they met the inclusion criteria of having a child with a suspected or formal diagnosis of autism, their child met criteria for PDA, and their child was prescribed fluoxetine in the last 2 years. In British Columbia, the province of the study, all individuals with a diagnosis of autism have had completion of the Autism Diagnostic Observation Schedule (ADOS-2) and the Autism Diagnostic Interview-Revised (ADIr),

Table 2

Results from demographic survey of participants’ children
Sex	11 male, 2 female (n = 13)
Age	Range: 6–13 years old Average age: 9.6
Co-occurring conditions	Generalised anxiety disorder or other unspecified anxiety disorder n = 10
	ADHD n = 7
	Sensory processing disorder n = 2
	Unspecified neurodevelopmental disorder n = 2
	Depression n = 1
	Oppositional defiant disorder n = 1
Medications	Methylphenidate n = 4
	Clonidine n = 2
	Guanfacine n = 2
	Lisdexamfetamine n = 2
	Melatonin n = 2
	Lorazepam n = 1
	Sertraline n = 1
	None n = 4

Data Collection

A mixed-methods approach was used. We surveyed parents via Qualtrics™ using the Extreme Demand Avoidance 8-item measure (EDA-8) to confirm and quantify PDA traits. Participants rated their child’s PDA features both before and after receiving fluoxetine on a 4-point Likert scale from ‘not true’ to ‘very true’ (Table 3). We conducted semi-structured interviews with participants over Zoom to collect qualitative data. All of the interviews were conducted with the mother of the child with PDA, however responses were representative of both parents’ perspectives. Questions were focused around the PDA behaviours and concerns that brought parents to see a paediatrician, thoughts or concerns of starting fluoxetine, adherence, and perceived benefits and side effects after starting fluoxetine. Please see appendix for interview questions.

Qualitative Data Analysis

Semi-structured interviews were recorded and transcribed. Examples of quotes were then imported into NVivo™, a software used for classifying, sorting and examining relationships in qualitative data used in thematic analysis. JZ and RL independently coded the transcripts using a combination of deductive and inductive coding which were then compared and discussed until consensus was reached.

Quantitative Data Analysis

Data from Qualtrics was downloaded into Excel™ for analysis. Descriptive statistics were calculated to summarise the data and two-tailed t-tests were conducted to compare behaviours before and after taking fluoxetine.

Survey results

Table 3

Results from EDA-8 Questionnaire Participants were asked to rate their child’s behaviour on a 4-point Likert scale of 1 = not true, 2 = somewhat true, 3 = mostly true, 4 = very true. * indicates P-values that were significant
	Mean before fluoxetine (± SD)	Mean after fluoxetine (± SD)	p-value
Obsessively resisting and avoiding ordinary demands and requests	3.38 ± 0.74	2.15 ± 0.66	< 0.05*
Being driven by the need to be in charge	3.46 ± 0.93	2.38 ± 0.84	< 0.05*
Telling other children how they should behave and feeling that these results did not apply to themselves	2.85 ± 1.1	2.31 ± 0.72	> 0.05
Having difficulties complying with demands unless they were carefully presented	3.62 ± 0.62	2.62 ± 0.84	< 0.05*
Being unaware of differences between themselves and authority figures (ex. parents, teachers)	2.23 ± 1.12	1.92 ± 0.83	> 0.05
Experiencing mood changes very rapidly (ex. switching from affectionate to angry in an instant)	3.08 ± 0.92	2.23 ± 0.89	< 0.05*
Using outrageous or shocking behaviour to get out of doing something	2.77 ± 0.97	1.77 ± 0.58	< 0.05*
Having bouts of extreme emotional response to small events (ex. crying, giggling, becoming furious)	3.77 ± 0.42	2.15 ± 0.86	< 0.05*

Results of thematic analysis

Theme 1: Significant impact of PDA profile on function

The majority of participants described a pattern of behaviours that profoundly disrupted their family dynamic and quality of life, including threats of self-harm, running away from home, breaking objects, threatening others with knives, or physical harm. Although their child may threaten to commit suicide, parents emphasized that these threats were a response to the demand and had no active intent to harm beyond resisting the demand placed on them. Participants would be recovering from the physical and emotional distress from the aggressive behaviours when their child would request affectionate embraces shortly after which was jarring and difficult for them to process. Two parents described being traumatized after physical harm from their child necessitated a call to the police, with one parent reporting this resulted in their child being handcuffed.

Most families also struggled with having their child at school for a variety of reasons: their child was too anxious to leave the house, would run away from school, or would display aggressive and defiant behaviours at school. Some parents spent hours attempting to separate from their child in an attempt to decrease their anxiety. Ultimately, they opted for homeschooling, but this choice reduced the time available for their other children, their careers, and their personal well-being. The intensity of resistance to demands forces constant supervision, causing emotional exhaustion and blurring parental roles; one parent described feeling that they had to constantly manage their child’s emotions in addition to their usual parenting tasks. Traumatic events involving authorities highlight the severity of these behaviours, while disrupted sleep and routines underscore the turmoil that these families experience.

Table 4

Participants describe the severity of their child’s PDA traits and impact on quality of life before starting fluoxetine
Theme	Examples of quotes
Defiant and aggressive behaviours	‘It's like her mind's telling her that she has to go to the extreme on the defiance, where she is now if you don't do this, I'm going to break this of yours, or I'm gonna kill you...The day before she was beat up at school by 3 boys, so she really didn't want to go to school, and instead of saying, ‘you know, mom, I don't want to go because of this,’ it went into full blown meltdown, and full blown defiance and ‘I'm gonna run away’...She damaged my door…she broke some stuff, and it was just escalating and escalating right. The defiance was not just the ‘no, I'm not doing this, I'm just gonna sit here like a lump,’ it's, ‘I'm gonna scream at the top of my head because I know it's gonna bother you, and then I'm gonna you know, break your phone and...you like this, so I'm gonna attack it.’
	‘When he would have big tantrum and it would involve…throwing things, breaking things, attempting to hit us, attempting to hurt us, attempting to his us with objects, attempting to run away, suicidal talk’
	‘Meltdowns and you know aggression and defiance and those kinds of things, those have been lifelong basically’
	‘Our son started to um throw things and started to shout things that were more incendiary, more hurtful things like um 'I want to kill her' 'I want to hurt them' 'I want to', you know. 'Don’t let me hurt them' kind of thing…he says to us often 'if I had to choose I wouldn’t come to this life' and 'if I had to choose you as parents I wouldn’t choose you as parents’
	'[my daughter] bit a police officer, she was spitting in their face. She was kicking. They were holding her down. She was throwing stuff. Another officer got hit with a pair of safety kids scissors in the head. They ended up pulling her off her bunk bed, and they…had to handcuff [her] 9 year old. It was very traumatic…'
	‘She had hit me multiple times with the wooden spoon. My forearms from elbows down were so bruised cause she was just hitting me over and over again cause she was trying to run away and trying to leave, and she had threatened me with a knife.’
	‘Aggressive behaviour range from hitting, kicking, biting, spitting, scratching, breaking things…just complete dysregulation. And kind of in a fight mode right?’
Effects on quality of life	'A lot of need on my part to be parent, teacher, emotion manager like all sorts of things for him'... '[I] ended up being in the classroom with [two kids with PDA] for the 6 hours a day for the 3 weeks and the teacher said to us, ‘I’m sorry they can’t return’ because neither of them are functioning although my older daughter was functioning but she couldn’t attend without her brother and I couldn’t attend with her.'
	‘He’d expressed he hated his life, he was deeply unhappy and distressed. But he hasn’t said anything like that since [starting medication]’
	'It was so hard for us to get him to school that we thought well he wears pyjamas to school at least he’s at school'
	‘Once a month I was getting together with other moms for dinner. It had been going on for years, right? So on those nights there was a sitter, there was an established pattern. He knew what to expect, and suddenly those became a big to-do'
	‘He’s going weeks without leaving the house. He had become completely nocturnal, and so we also were having a lot of challenges where he was up throughout the night doing things we didn't want him doing while we were sleeping…he was waking us in the night, so none of us were getting good sleep. And then through the day, he was expecting us to be completely silent so he could sleep, and if he was getting woken he would immediately lash out.’

Theme 2: Anxiety underlies disruptive behaviours in children with PDA

The majority of participants indicated that their child had an anxiety disorder that was severe in nature. Participants found that the majority of their child’s disruptive behaviours were associated with or were a direct manifestation of their child’s anxiety in different settings. For example, when asked about why their child pushing other kids or would refuse to leave the house, participants noted their child was anxious being around other children or overwhelmed by social situations. Other behaviours consistent with a PDA profile such as having a meltdown about other people hurting themselves, hitting or pushing other children when they get close, and tantrums in social situations were also described by parents as related to their child’s anxiety.

Table 5

Participants describe anxiety underlying their child’s disruptive behaviours prior to starting fluoxetine
Theme	Examples of quotes
Severity of anxiety	'Severe, for lack of a better description, anxiety.'
	'Off-the-chart anxiety'
Anxiety underlying disruptive behaviours	'Anxiety and startledness, worrying about stuff before it happens. Worrying about things when he sees it happen. Like he always thinks people are going to hurt themselves and freaks out.'
	'He was really anxious around other children. If anybody got too close he would lash, lash out and often hit or push.'
	'Before he took fluoxetine the main symptoms were depression, high anxiety to the point that he couldn’t go out, like couldn’t literally could not go out of the house and would not go out of the house so our whole family was totally housebound'
	'Overwhelmed by some social situations, high amount of anxiety around that which then would lead to a lot of…problem behaviour like throwing things, aggression, hiding behind things...just kind of big tantrums more than what should be expected.’
	‘Would choose to pee in one of his toy boxes, pee in the front room, pee in the floor of his bedroom and it became a thing…even when [their brother] wasn’t screaming…[our] youngest one being born and the diversion of attention was kind of creating a lot of anxiety for [our son with PDA]’

Theme 3: Participants’ motivation to try fluoxetine and worries about medicating their child

Most participants were motivated to start a medication to manage their child’s mental health and behaviours, with many feeling at “wits’ end” and expressing a desire to connect with their children. Prior to initiating fluoxetine, participants had tried occupational therapy, behavioural therapy, and other non-pharmacologic therapies with minimal success. Many described feeling desperate and worried that they were running out of options. All participants reported having no reservations against fluoxetine specifically, but some participants had reservations towards medicating their child due to social stigma or misconceptions regarding what medications would do to their child. Some parents were concerned about side effects such as dependence, or worried that medications would turn their child into a ‘zombie’, and wondered whether the medication would make any difference. One parent also described feeling guilty over medicating their child as they felt that the escalating behaviours would have been prevented if they had been a stricter parent. However, all parents were reassured after discussing their concerns with AR and parents consistently expressed a desire to trial a medication to avert crises and to minimize family harm.

Table 6

Participants’ thoughts prior to their child starting fluoxetine
Theme	Examples of quotes
Fear and social stigma of medicating their child	'I had people massively, dramatically warn me against how if you put your child on medication they’re never gonna be the same, they’re gonna be a zombie...and it terrified both my ex-husband and I about it....I might have sought help sooner if I hadn’t had the fear of medications drilled into me’
	'My husband and I…grew up in an age where you don’t drug your children, so we were both very hesitant'
	'I was anti-medication…more so I just think for socially stigmatizing reasons.'
	‘I wasn’t concerned about specific drugs but just about medicating a child who was that young... you know, ingrained thing that probably was a social bias. They shouldn’t be medicated…partly because you know there’s people in my family who think I should have been tougher on him right. If I was just a more stricter parent then he wouldn’t have had all these outbursts and problems...so that was in the back of my mind a little.”
	‘My child’s been very sensitive to medication. He hasn’t done well on umm on like stimulant medications to help manage the ADHD symptoms...I’m always worried about umm side effects or um any codependent tendencies that arise yeah’
	‘I was looking forward to it, you know, cause we had some positive things with it, right? So I wasn't really nervous. We just wanted, you know. I just feel so bad, for you know the kids got a rough deal, and I want a sense of regularity for her.’
	‘I’m not against medications, I also like…if it’s not needed then it doesn’t make sense to stay on it forever’
	‘I was quite concerned about side effects. That was my biggest fear with putting him on was the side effects and whether it would make a difference or not, and how hard like having to go on and off like tapering on tapering off you know.’
Desperation for a solution	'His mental health was desperate, it was a serious crisis. And he needed help, so we were quite happy to try whatever you know, an expert suggested.'
	'We were hitting a crisis point with…our son’s behaviour that we were willing to try fluoxetine'
	‘First of all like the idea of the chemical was for me, was really upsetting to us. So that's - that wasn't somewhere we wanted to go. But at the same time we also really concerned about what was going to happen without something...At the point that we started it, we were actually really close to police involvement. So neither my husband nor I…super comfortable with medication in general, but it felt like necessary’
	‘At that point I was just like ... .I'll try anything cause he just…you know he ended up…I think he started like 3 or 4 days before he ended up being kicked out of school for good so at that point we were in crisis right?’
	'We weren’t able to go beyond those mood swings to really connect with him.'
	'Occupational therapist…can’t work with [my child] anymore [unless I] get to the root of why [my child] gets dysregulated.'

Theme 4: Overall improvement in behaviour with fluoxetine with minimal side effects

The majority of participants saw an improvement in their child’s behaviour within a few weeks of initiating fluoxetine with their child being better able to communicate and self regulate prior to having a meltdown. Participants noticed a significant reduction in the frequency of meltdowns that resulted in physical or emotional harm but did not notice any change in the intensity of the behaviours during meltdowns. Overall, participants reported a significant improvement in function and quality of life after initiation of fluoxetine; their child was able to leave the house, would make fewer statements about wanting to harm themselves and others, and that despite their child still feeling worried or anxious, they were better able to manage these emotions.

The benefit of fluoxetine was dose dependent in some cases. A child had a reduction in dose and “started scratching [their parent] and kicking [them] and just completely lost it”, and behaviours again improved once the dose was subsequently increased.

The majority of participants reported that their child did not experience side effects while being on fluoxetine. Those who did found that the side effects did not significantly impact quality of life and were outweighed by the benefits provided by the medication.

Table 7

Participants describe their child’s behaviours after starting fluoxetine
Theme	Examples of quotes
Improved self-regulation	'A life saver. It was definitely a family saver because now our child is able to have a 5 to 10 second pause…to think and respond differently instead of instantly attacking someone…in the past…he would go for the jugular like he knew what the things were that you were insecure about.'
	'He used to 100% of the time be shout first...calm down, talk it out later…and now let’s call it at least 70% of the time he’s able to communicate.'
	'More calm. Less anxious…just less quick to react. So like, when he’s like… boom… he’s in fight mode, he’s not so quick to get to that point anymore.'
	'Really helped for the anxiety piece I think. I do think prior to taking it he was fighting more nonverbally and you could see it in his body, you know, when something was bothering him. Now he’ll say 'don’t run stop' that kind of thing, but it’s less often and I also feel like it’s less severe. Before, if his sister was running in the park and his sister would get too close to the road, right, he would scream so loudly. He would physically go after her. Now it’s like 'hey don’t run on to the road.'
Decrease in suicide ideation	'On any given day that could be enough for it all to go downhill even to the point of full blown escalation, suicidal talk, harming us but after fluoxetine the frequency has gone down.'
	'Expressed he hated his life, he was deeply unhappy and distressed. But he hasn’t said anything like that since June.'
Improvement in function	'It wasn’t until he got on the right dose of fluoxetine that he would go to the beach and ride his bike, and you know, leave the house…fluoxetine is playing a role now in kind of keeping him emotionally steady.'
	'He wasn’t threatening to hurt himself or kill himself as much.'
	'He still gets worried about a lot of things…the world is quite scary I guess for him. But he doesn’t have those mood swings…sometimes it happens, maybe once a week or once every two weeks we have a big crisis. But it was happening twice a day before. So it’s very different. It’s much more manageable when it’s not as frequent'

Table 8

Side effects experienced by participants’ children while on fluoxetine
No side effects	n = 8
Fatigue	n = 2
'Heightened emotional intensity'	n = 1
Insomnia	n = 1
Nightmares	n = 1
Weight gain	n = 1

In this small community-based study that sought to quantify what was an anecdotal clinical practice, our findings demonstrate an overall positive impact of fluoxetine in improving function in children and youth who experience pronounced PDA symptoms. Overall, responses to demands were significantly improved with children being less likely to have extreme behaviours and caregivers felt they were able to redirect or calm their child down more frequently. For parents, this benefit translated to improved family function. Furthermore, there were limited side effects and there was a dose response to fluoxetine in some cases, with higher doses yielding improved responses and function.

No current pharmacologic treatment options for PDA

Management of PDA generally involves behavioural interventions and treatment of co-occurring psychiatric disorders [12]. Evidence for pharmacologic therapies is significantly limited and the majority of caregivers expressed a sense of being overwhelmed by the lack of options prior to seeking guidance from a paediatrician to explore pharmacologic therapy. In spite of a lack of evidence-based guidance in managing PDA, clinicians tend to reach for pharmacotherapies that have been effective in similar situations. Fung et al. (2016) conducted a systematic review and meta analysis of 46 RCTs for IA and found that antipsychotics, valproate, amantadine, SSRIs, N-acetylcysteine, clomipramine, and omega-3 fatty acids had some benefit [6]. Specifically, the antipsychotics risperidone and aripiprazole were the most effective agents. However, these have well-documented, significant and long term adverse effects that must be closely monitored, including sedation, weight gain/obesity, and increased risk of extrapyramidal symptoms such as akathisia, dystonias, tremor, tardive dyskinesia [13]. The differences between IA and PDA are not well-appreciated in the literature, so applying IA treatment principles may not address the underlying etiology in PDA, which we propose trigger the aggression and meltdowns. For these reasons, we suggest that consideration should be given to the use of anxiolytics for patients with PDA exhibiting aggressive behaviours before medications for aggression such as antipsychotics.

Fluoxetine as an effective treatment

Fluoxetine is commonly used off-label in Canada to treat paediatric anxiety due to its long half-life (minimising potential withdrawal symptoms) and availability in both capsules and oral suspension (improving the ease of titration and administration). In a review of the literature, evidence for the use of fluoxetine in PDA is lacking, with scarce reports noted in patient interviews [14]. Despite this study’s limitations (especially the small sample size), it was encouraging to see that most participants responded well to fluoxetine. This was notable as fluoxetine’s effect in the paediatric population is generally considered to be modest when used solely for the purpose of managing features of anxiety. For example, a meta-analysis found that several SSRIs had a moderate magnitude of efficacy in paediatric patients with anxiety (Cohen's d = 0.62, confidence interval: 0.34–0.89, P = .009) and there was evidence of modest heterogeneity (I2 = 0.29, P = 0.103) [15]. The level of improvement of anxiety in patients with PDA seen in this study should encourage further investigation as a promising therapeutic choice.

The adverse effects of fluoxetine in children with ASD are generally mild, with the most common being mood disturbance, gastrointestinal upset, and sleep disorders, which are all often comparable to placebo [16]. The US Food and Drug Administration has a black box warning regarding the use of SSRI’s as an analysis of short-term placebo-controlled trials found that there was a greater risk of suicidality during the first few months of treatment in children and adolescents receiving antidepressants compared to the placebo group [17]. We found that most participants did not note any side effects, but those that did reported they were mild and were favourable when compared to the benefits of initiating fluoxetine.

Reframing PDA as severe form of anxiety

The behaviours in PDA are usually associated with high levels of anxiety and the need for control is often attributed to anxiety. This may be rooted in a variety of factors, such a fear of failure, or a heightened sensitivity to sensory stimuli. While we understand that PDA is complex with its own spectrum that is not fully understood, we put forth that the ‘disruptive behaviours’ are extreme expressions of the individual's underlying anxiety rather than due to autism, another medical condition, or unreasonable caregiver requests.

As children and youth with ASD often struggle with social communication, their anxiety presents differently than in a neurotypical patient, so children with PDA would therefore score differently on rating scales for paediatric anxiety, such as the Screen for Child Anxiety Related Disorders (SCARED). In addition, in children with diagnoses of autism, outbursts and aggressive behaviours tend to be attributed to the autism and overshadow the underlying anxiety. The use of a modified version of the Childhood Anxiety Sensitivity Index (CAS-I) may be of benefit to clinicians who are new to working with children with PDA to support treatment of anxiety prior to the ‘disruptive behaviours’.

The symptoms of PDA cause significant challenges to the patient and their families, with the majority of participants dedicating significant portions of their days to being emotional and behavioural support for their child on top of their regular duties as a parent. Caregivers may find relief in knowing that their child is neurologically unable to comply with requests and demands, rather than doing so out of malice. The majority of participants’ children had a diagnosis of an anxiety disorder, which may explain why fluoxetine was so effective in improving behaviours in this cohort as the anxiety (which is driving their behaviours) was finally being treated. However, we do not see these as distinct diagnoses because as the anxiety disorder was treated, the PDA symptoms also significantly improved, suggesting that PDA could be a physical manifestation of anxiety in children with autism.

Limitations

This study was initially conceived as a “practice to evidence” small retrospective cohort study for AR’s practice when enough patients with similar presentation and responses were seen; this has resulted in a small sample size. Given the community-based practice, built on a relational approach and grounded in trust, AR’s preconceptions could have influenced participants interpretation of the results, resulting in bias. Furthermore, parents who did not find fluoxetine effective may have been less likely to respond to invitations for participation in the study (n = 9). Additionally, communication with parents regarding the benefits of fluoxetine in PDA during consent for the study may have influenced their interview responses. Another potential source of error is the reliance on parental recollection of symptoms prior to the initiation of fluoxetine, however, this is a common psychiatric methodology.

We suggest future prospective studies to compare outcomes between antipsychotics such as risperidone or aripiprazole with fluoxetine in decreasing disruptive behaviours in children with PDA and to incorporate multiple sites into their study.

The EDA-8 questionnaire adapted for the semi-structured interviews was originally designed to measure PDA traits, but was not designed for measuring changes to these traits with treatment. We suggest that future studies identify and validate a standardized method to measure treatment response for PDA. We also recommend the use of an anxiety disorder screening tool such as a modified version of the Childhood Anxiety Sensitivity Index in conjunction with a standardized method to measure treatment response for PDA. Due to the retrospective nature of this study, we were not able to compare the baseline level of anxiety that participants’ children experienced before and after initiation of fluoxetine.

No funds, grants, or other support was received. This study is self-funded.
One of the authors is the paediatrician at the medical clinic where interviewees were recruited and was not aware of the identity of participants. Participants were informed, in writing, that their participation was voluntary and that they retain the right to withdraw or refuse to participate without any negative consequences to their medical care.
No AI generated tools were used in the creation of this manuscript.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the University of British Columbia Behavioural Research Ethics Board (November 29, 2022/No. H22-02961).

Consent to participate and publish

Written informed consent to participate and consent to publish anonymized data were obtained from all individual participants included in the study.

Data availability statement

The data that support the findings of this study are openly available in Mendeley data at http://doi.org/10.17632/pmrs2syg76.1.

O’Nions, E., Viding, E., Greven, C. U., Ronald, A., and Happé, F. 2014. Pathological demand avoidance: Exploring the behavioural profile. Autism: The International Journal of Research and Practice, 18(5), 538–544. https://doi.org/10.1177/1362361313481861 PDA Society 2022. Identifying & Assessing a PDA profile - Practice Guidance [pdf]. Available at:<https://www.pdasociety.org.uk/wp-content/uploads/2023/02/Identifying-Assessing-a-PDA-profile-Practice-Guidance-v1.1.pdf> [Accessed 8 August 2023].
Green, J., Absoud, M., Grahame, V., Malik, O., Simonoff, E., Le Couteur, A., and Baird, G. (2018). Pathological Demand Avoidance: symptoms but not a syndrome. The Lancet. Child & adolescent health, 2(6), 455–464. https://doi.org/10.1016/S2352-4642(18)30044-0
Egan, V., Linenberg, O., and O'Nions, E. (2019). The Measurement of Adult Pathological Demand Avoidance Traits. Journal of autism and developmental disorders, 49(2), 481–494. https://doi.org/10.1007/s10803-018-3722-7
Newson, E., Maréchal, K. L., and David, C. 2003. Pathological demand avoidance syndrome: A necessary distinction within the pervasive developmental disorders. Archives of Disease in Childhood, 88(7), 595–600. https://doi.org/10.1136/adc.88.7.595
Kamp-Becker, I., Schu, U., and Stroth, S. 2023. Pathological Demand Avoidance – aktueller Forschungsstand und kritische Diskussion. Zeitschrift Für Kinder- Und Jugendpsychiatrie Und Psychotherapie. https://doi.org/10.1024/1422-4917/a000927
Fung, L., Mahajan, R., Nozzolillo, A., Bernal, P., Krasner, A., Jo, B., Coury, D., Whitaker, A., Veenstra-VanderWeele, J., and Hardan, A. 2016. Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis. Pediatrics, 137, S124–S135. https://doi.org/10.1542/peds.2015-2851K
Milton, D. 2013. 'Natures answer to over-conformity': Deconstructing Pathological Demand Avoidance [Internet publication]. Autism Experts. Available at: https://kar.kent.ac.uk/62694/431/Natures%20answer%20to%20over%20conformity.pdf. [Accessed 8 August 2023].
Truman, C., Crane, L., Howlin, P., and Pellicano, E. 2021. The educational experiences of autistic children with and without extreme demand avoidance behaviours. International Journal of Inclusive Education, 0(0), 1–21. https://doi.org/10.1080/13603116.2021.1916108
Christie, P. 2007. The Distinctive Clinical and Educational Needs of Children with Pathological Demand Avoidance Syndrome: Guidelines for Good Practice. Good Autism Practice (GAP), 8(1), 3-11.
Kent, J. M., Kushner, S., Ning, X., Karcher, K., Ness, S., Aman, M., Singh, J., and Hough, D. 2013. Risperidone dosing in children and adolescents with autistic disorder: A double-blind, placebo-controlled study. Journal of Autism and Developmental Disorders, 43(8), 1773–1783. https://doi.org/10.1007/s10803-012-1723-5
Lucchelli, J. P., and Bertschy, G. 2018. Low-Dose Fluoxetine in Four Children with Autistic Spectrum Disorder Improves Self-Injurious Behavior, ADHD-Like Symptoms, and Irritability. Case Reports in Psychiatry, 2018, 6278501. https://doi.org/10.1155/2018/6278501
O’Nions, E., Eaton, J. 2020. Extreme/‘pathological’ demand avoidance: An overview. Paediatrics and Child Health, 30(12), 411–415. https://doi.org/10.1016/j.paed.2020.09.002
Loy, J. H., Merry, S. N., Hetrick, S. E., and Stasiak, K. 2017. Atypical antipsychotics for disruptive behaviour disorders in children and youths. The Cochrane Database of Systematic Reviews, 2017(8), CD008559. https://doi.org/10.1002/14651858.CD008559.pub3
Rutter, N. 2023. Rupture, repair, the loss and re-construction of identity: Seeking support in situations of adolescent-to-parent violence and abuse. Frontiers in Health Services, 3, 1139727. https://doi.org/10.3389/frhs.2023.1139727
Strawn, J. R., Welge, J. A., Wehry, A. M., Keeshin, B., & Rynn, M. A. (2015). EFFICACY AND TOLERABILITY OF ANTIDEPRESSANTS IN PEDIATRIC ANXIETY DISORDERS: A SYSTEMATIC REVIEW AND META-ANALYSIS: Research Article: Pediatric Anxiety Meta-Analysis. Depression and Anxiety, 32(3), 149–157. https://doi.org/10.1002/da.22329
Reddihough, D. S., Marraffa, C., Mouti, A., O’Sullivan, M., Lee, K. J., Orsini, F., Hazell, P., Granich, J., Whitehouse, A. J. O., Wray, J., Dossetor, D., Santosh, P., Silove, N., and Kohn, M. 2019. Effect of Fluoxetine on Obsessive-Compulsive Behaviors in Children and Adolescents With Autism Spectrum Disorders: A Randomized Clinical Trial. JAMA, 322(16), 1561–1569. https://doi.org/10.1001/jama.2019.14685
Center for Drug Evaluation and Research. (2018). Suicidality in children and adolescents being treated with antidepressant medications. U.S. Food and Drug Administration. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/suicidality-children-and-adolescents-being-treated-antidepressant-medications

No competing interests reported.

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Parental experiences in the use of fluoxetine for management of ‘disruptive behaviours’ in children and youth with autism and pathological demand avoidance – a mixed methods exploratory study (Fluoxetine study)

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Abstract

Background

Methods

Results

Conclusion

Figures

Introduction

PDA - the diagnostic dilemma

Methods

Participants

Data Collection

Qualitative Data Analysis

Quantitative Data Analysis

Results

Survey results

Results of thematic analysis

Theme 1: Significant impact of PDA profile on function

Theme 2: Anxiety underlies disruptive behaviours in children with PDA

Theme 3: Participants’ motivation to try fluoxetine and worries about medicating their child

Theme 4: Overall improvement in behaviour with fluoxetine with minimal side effects

Discussion

No current pharmacologic treatment options for PDA

Fluoxetine as an effective treatment

Reframing PDA as severe form of anxiety

Limitations

Declarations

References

Additional Declarations

Supplementary Files

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