Alcohol craving (craving) or the urge to consume alcohol is a characteristic so pervasive in those with Alcohol Use Disorder (AUD) that it is included as a diagnostic criterion (DSM-5) exhibited by 54–72 % of diagnosed individuals (Chakravorty et al., 2010), and is a therapeutic target in the behavioral and pharmacological treatment of AUD. Craving may be associated with drinking, demonstrating its importance in the context of AUD treatment (Chakravorty et al., 2010). Insomnia is another clinically significant condition that occurs in 36–91 % of patients with AUD, (Brower et al., 2011, Chakravorty et al., 2016, Kolla et al., 2020). This co-occurring insomnia is associated with a higher intensity of AUD, alcohol consumption, craving (Chakravorty et al., 2016, He et al., 2019), and an increased risk of relapse in early recovery from drinking in AUD (Brower, 2003).

Craving has also been directly associated with disturbed sleep in some preliminary clinical studies (Brooks et al., 2019, Kolla et al., 2020). The relationship between craving and disturbed sleep may have an underlying neurobiological basis. Sleep continuity disturbance has been independently associated with decreased activation of the prefrontal cortex [PFC, (Altena et al., 2008)] and impaired reward-processing behavior (Gujar et al., 2011, Mullin et al., 2013). The PFC’s inability to modulate mood disturbance in insomnia and emotion-triggered alcohol-seeking behavior may activate circuits in the basal ganglia that lead to obsessive and compulsive aspects of craving and heavy drinking (Seo & Sinha, 2014). Further complicating these associations is the Ventral Tegmental Area’s (VTA’s) connection with the orexinergic neurons in the lateral hypothalamus that promote wakefulness when activated (Saper, Scammell, & Lu, 2005). Stimulated Orexin 1 receptors increase the motivation for alcohol and substance use, and antagonism of these receptors decreases stress-induced alcohol-seeking behaviors in animals (Campbell et al., 2020). The above information shows that dysfunction of the nucleus accumbens, prefrontal cortex, and the orexinergic neurons can lead to sleep disturbance, craving, compulsive alcohol intake that is driven by substantially decreased rewarding feelings, and mood disturbance.

A recent pilot study demonstrated a direct and positive association between alcohol craving and insomnia symptoms, and quetiapine decreased craving in those with insomnia symptoms (He et al., 2019). Quetiapine, an atypical antipsychotic medication approved by the Food and Drug Administration to treat Schizophrenia and Bipolar Disorder is an antagonist of the dopamine (D1 and D2), serotonin (5HT2A), adrenergic (α1 and α2), histamine (H1), and orexin A receptors. Quetiapine is frequently used to treat craving and insomnia in patients with substance use disorders on an “off-label” basis and has been shown to improve sleep quality and continuity in AUD (Chakravorty et al., 2014, Litten et al., 2012). Thus, craving and insomnia may be directly associated with each other as part of an acute or subacute alcohol withdrawal syndrome after an abrupt cessation or a decrease in alcohol use, and treatments like quetiapine may modify both these clinical features, thereby offering promise to decrease the risk of alcohol consumption in AUD (Brooks et al., 2021, Chakravorty et al., 2010, Miller et al., 2017).

He and colleagues conducted the first investigation that directly evaluated this relationship between craving and insomnia and whether quetiapine treatment improved craving and insomnia (He et al., 2019). They investigated this relationship using the Penn Alcohol Craving Scale (PACS) to evaluate craving and the short sleep index (SSI) to evaluate insomnia symptoms in a sample of treatment-seeking patients with alcohol dependence (moderate – severe AUD). Their cross-sectional analysis showed that craving was positively associated with difficulty falling asleep and the SSI total score. Treatment with quetiapine in the subgroup of subjects with insomnia symptoms showed a relatively steeper decline in the PACS total score, relative to the subgroup without insomnia symptoms at baseline. Thus, this study showed a positive relationship between craving and insomnia symptoms. Furthermore, treatment with quetiapine differentially improved craving in those complaining of insomnia symptoms at baseline. Additional investigations are needed to demonstrate that this relationship between alcohol craving and insomnia also exists among those with co-occurring AUD and insomnia disorder (insomnia, a disorder with impaired daytime functioning), and the role of quetiapine treatment in improving insomnia severity and craving.

The current study extends the existing literature by re-evaluating this relationship between craving and insomnia in a larger sample of subjects with AUD, utilizing an insomnia rating scale commonly used in clinical practice, and evaluating the effect of quetiapine on insomnia and craving. We hypothesize that treatment with quetiapine will be associated with a greater improvement in insomnia and craving in those with insomnia at baseline, relative to the other groups, and that these improvements will be reversed after end of treatment. Positive results will help clinicians better understand this relationship and guide them with evidence-based treatment options in patients with co-occurring insomnia and AUD, a subgroup of patients with AUD who are at a higher risk of adverse health outcomes (Chakravorty et al., 2016).