Scopolamine in Bipolar Depression

Inclusion Criteria

To be eligible for inclusion, each participant must meet all of the following inclusion criteria at Screening (Visit 1) and must continue to fulfil these criteria at Visit 2 to take part in the trial:

• Diagnosis of Bipolar Disorder according to Diagnostic Statistics Manual (DSM)-V criteria
• Experiencing an episode of depression of at least moderate severity at Visit 1 (Screening) and Visit 2 based on clinical interview by a trained clinician and a Hamilton Depression Rating Scale (HDRS) score ≥ 14.
• ≥ 18 years old at Visit 2 (male or female)
• In the opinion of the Principal Investigator or Sub Investigator's, be able and willing to provide written informed consent and to comply with the requirements of this study protocol.
• Written informed consent prior to participating in the study
• Urea and Electrolytes (U&Es), Liver Function Tests (LFTs) and Thyroid Function Tests (TFTs) laboratory tests within acceptable ranges in the previous 4 months of the Screening Visit (Visit 1).

Placebo run-in inclusion criteria at Randomisation visit (Visit 3):

• In addition to above, participants must be experiencing an episode of depression of at least mild severity (having previously experienced an episode of moderate depression at Visit 2 with HDRS ≥14), based on clinical interview by a trained clinician and a HDRS score of ≥ 8.

Exclusion Criteria

Participants who meet any one or more of the following exclusion criteria at Screening (Visit 1) or the Visit 2 will not be eligible to take part in the trial:

• History of other Axis I diagnosis (including Recurrent Depressive Disorder or Psychotic Disorders such as schizo-affective disorder, conditions that can also present with depressive episodes)
• History in the three months prior to Visit 2 of alcohol dependence syndrome or substance dependence syndrome.
• Current use of oral steroid at Visit 1
• A confirmed diagnosis of dementia
• A diagnosis of intellectual disability (IQ 6) at screening or Visit 2.
• Presence of an established neurological disorder or other serious demyelinating conditions as determined by the treating physician (e.g. space occupying lesion, multiple sclerosis)
• Current involuntary detention under the Mental Health Act (MHA) 2001 in an acute psychiatric inpatient unit
• Severity of Bipolar Disorder is such that participation in a clinical trial is not appropriate because of the risk of imminent self-harm (based on clinical note review and review at screening visit by experienced clinician)
• A history of an allergic reaction or sensitivity to Scopolamine (Hyoscine Hydrobromide). Participants will be asked at the screening visit about any previous treatment with scopolamine (Hyoscine Hydrobromide) to ascertain any previous allergic reaction or sensitivity to this agent.
• A clinical diagnosis of narrow angle glaucoma, myasthenia gravis, paralytic ileus,pyloric stenosis, toxic megacolon and acute porphyria.
• Individuals will be excluded from the study if currently prescribed anticholinergic medications, including Physostigmine, Biperiden and Procyclidine. Individuals will additionally be excluded if currently prescribed Tricyclic Antidepressants which are associated with significant anticholinergic properties (e.g. Amitriptyline and Nortriptyline) that are currently causing the participant to experience anticholinergic side effects (e.g. blurred vision, constipation, urinary retention, cognitive difficulties). No individuals will have anticholinergic medications stopped to allow them enter the trial.
• Bradycardia 100bpm or hypotension (systolic BP 6).
• A Serious Adverse Event (SAE) experienced during infusion which required medical intervention and whereby attending physician deemed it inappropriate for the participant to engage in future infusions.