Akathisia, a common side effect of psychotropic medications, poses a significant challenge in neuropsychiatry, affecting up to 30% of patients on antipsychotics. Despite its prevalence, akathisia remains poorly understood, with difficulties in diagnosis, patient reporting, and treatment efficacy. This research aimed to shed light on effective interventions to improve akathisia management.

A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted, encompassing controlled trials in English and Italian languages. Databases, such asPubMed, Scopus, and EMBASE, were searched until July 9, 2023. Treatment effectiveness was assessed using standardized mean differences (SMDs) in post-treatment akathisia scores.

Thirteen studies involving 446 individuals met the inclusion criteria. Benzodiazepines, beta-blockers, and NaSSA demonstrated significant efficacy as compared with placebo. Anticholinergic, anticonvulsant, triptan, and other treatments did not show significant differences. Benzodiazepines ranked highest in P-scores (0.8186), followed by beta-blockers and NaSSA.

Effective management of akathisia is crucial, with benzodiazepines, beta-blockers, and NaSSA offering evidence-based options. Treatment rankings provide guidance for clinicians. Future research should prioritize larger, more robust studies to address limitations associated with small sample sizes and publication bias. This research enhances our understanding of interventions for akathisia, offering promising options to improve patient quality of life and prevent complications related to non-adherence and mismanagement.

Akathisia is a relatively common adverse effect of antipsychotics although some second-generation antipsychotics are known to have a lower liability for the condition. The core feature of akathisia is mental unease characterized by a sense of agitation, usually accompanied by motor restlessness, which can cause patients to pace up and down and be unable to stay seated for more than a short time. An association between this discomfiting subjective experience and suicidal ideation has been postulated but remains uncertain.

Our aim is to perform a non-systematic review of the literature regarding the current understanding of antipsychotic-induced akathisia and its management.

A semi-structured review was conducted on Pubmed concerning the relationship between akathisia and antipsychotics.

All antipsychotics drugs can cause akathisia. The management of antipsychotic-induced akathisia should include a dose reduction of the antipsychotic treatment or a switch to quetiapine or olanzapine. If ineffective, a trial with propranolol may be useful as well as the addition of a 5-HT2A antagonist like mirtazapine or mianserine. At last the inclusion of a benzodiazepine may be helpful albeit the risk of dependence and anticholinergics mainly when other extrapyramidal symptoms are present.

High‐dose antipsychotic medication, antipsychotic polypharmacy and rapid increase in antipsychotic dosage should be avoided to prevent akathisia. There is limited evidence for any pharmacological treatment for akathisia such as switching to an antipsychotic medication with a lower liability for the condition, or adding a beta‐adrenergic blocker, a 5‐HT2A antagonist or an anticholinergic agent although some patients may benefit from such interventions.

Motor abnormalities (MAs) are the primary manifestations of schizophrenia. However, the extent to which MAs are related to alterations of subcortical structures remains understudied.

We aimed to investigate the associations of MAs and basal ganglia abnormalities in first-episode psychosis (FEP) and healthy controls. Magnetic resonance imaging was performed on 48 right-handed FEP and 23 age-, gender-, handedness-, and educational attainment-matched controls, to obtain basal ganglia shape analysis, diffusion tensor imaging techniques (fractional anisotropy and mean diffusivity), and relaxometry (R2*) to estimate iron load. A comprehensive motor battery was applied including the assessment of parkinsonism, catatonic signs, and neurological soft signs (NSS). A fully automated model-based segmentation algorithm on 1.5T MRI anatomical images and accurate corregistration of diffusion and T2* volumes and R2* was used.

FEP patients showed significant local atrophic changes in left globus pallidus nucleus regarding controls. Hypertrophic changes in left-side caudate were associated with higher scores in sensory integration, and in right accumbens with tremor subscale. FEP patients showed lower fractional anisotropy measures than controls but no significant differences regarding mean diffusivity and iron load of basal ganglia. However, iron load in left basal ganglia and right accumbens correlated significantly with higher extrapyramidal and motor coordination signs in FEP patients.

Taken together, iron load in left basal ganglia may have a role in the emergence of extrapyramidal signs and NSS of FEP patients and in consequence in the pathophysiology of psychosis.

Safety and tolerability of long-term treatment with the long-acting antipsychotic aripiprazole lauroxil (AL) were evaluated in patients with schizophrenia.

This was an international, multicenter, phase 3, 52-week safety study of 2 fixed doses of AL (441 mg or 882 mg intramuscular every 4 weeks). Safety endpoints included adverse events (AEs) and extrapyramidal symptoms (EPS) including akathisia, injection-site reactions (ISRs), and clinically relevant changes in metabolic and endocrine values.

Of 478 patients entering this study, 236 (49%) continued from a previous 12-week, phase 3 efficacy study of AL, and 242 (51%) were newly enrolled. Overall, 77% and 23% of patients received AL 882 mg (N = 368) and 441 mg (N = 110), respectively. AEs occurred in 50.4% of patients; most were mild (28.7%) or moderate (18.2%). The most common AEs were insomnia (8.4%) and increased weight (5.0%). Akathisia was reported as an AE in 3.8% of the overall population, with higher rates in patients initiating AL on study entry than those continuing on AL. EPS-related AEs occurred in 9.4% of patients, and AEs related to metabolic parameters were reported in 4.6% of patients. Weight gain was minimal (0.8 kg), and no clinically relevant changes were observed for metabolic parameters. The overall incidence of ISRs was 3.8%; most were associated with the initial injections in patients receiving their first injection in this study.

Long-term treatment with AL is generally well tolerated, with a safety profile consistent with that of oral aripiprazole. It is a suitable option for patients with schizophrenia.

This is a case-control study to investigate the prevalence, characteristics, and risk factors of pain in patients with Parkinson's disease (PD).

A total of 200 PD patients from eastern China were enrolled in our study. Accordingly, 200 healthy elderly adults were recruited as controls. The characteristics of pain were collected by using the Visual Analog Scale, Brief Pain Inventory (BPI), SF-36 Bodily Pain Scale, Unified Parkinson's Disease Rating Scale, Hoehn–Yahr Scale (H-Y), Hamilton Depression Scale, and Leeds Assessment of Neuropathic Symptoms and Signs.

Of the 200 PD patients, pain was complained by 106 patients (53%). According to the SF-36 Bodily Pain Scale, pain morbidity in PD patients was significantly higher than in the control group. The average pain during last 24 h measured by the BPI was 2.67. About 76% of PD patients were found to have one pain type, 21.7% were having two pain types, and 1.9% had three pain types. Further, 69.8% of these patients were presented with musculoskeletal pain, 4.7% with dystonic pain, 22.6% with radicular-neuropathic pain, 20.8% with central neuropathic pain, and 9.4% with akathisia pain. The onset age and depression were the most significant predictors of pain in PD patients (p < 0.05). However, there was no significant association between pain and gender, age, disease duration, or severity of the disease. Only 5.7% of PD patients with pain received treatment in this study.

Pain is frequent and disabling, independent of demographic and clinical variables, and is significantly more common in PD patients.

Akathisia is a neuropsychiatric syndrome characterized by subjective and objective restlessness. It is a common side effect in patients taking antipsychotics and other psychotropics. Patients with delirium are frequently treated with antipsychotic medications that are well known to induce akathisia as a side effect. However, the prevalence, phenomenology, and management of akathisia in patients with delirium remain largely unknown. The purpose of this review was to examine the medical literature in order to establish the current state of knowledge regarding the prevalence of antipsychotic-induced akathisia in patients with delirium.

A systematic review of the literature was conducted using the EMBASE, MEDLINE, PsycINFO, and CINAHL databases. Ten studies addressing the incidence of akathisia in patients taking antipsychotic medication for delirium were identified and included in our review.

The included studies reported a variable prevalence of antipsychotic-induced akathisia. A higher prevalence was found in patients taking haloperidol. Among atypical antipsychotics, paliperidone and ziprasidone were associated with a higher risk of akathisia. The risk for akathisia appeared to be a dose-related phenomenon.

Studies using specific scales for evaluation of akathisia in delirium are lacking. Some populations, such as patients with cancer or terminally ill patients in palliative care settings taking antipsychotics for the treatment of delirium, could be at higher risk for development of akathisia as a side effect.

Long-term use of the atypical antipsychotic iloperidone has not been investigated at doses above 16 mg/d. This article describes safety and tolerability results from the 25-week open-label extension of a 4-week placebo- and ziprasidone-controlled clinical trial of iloperidone.

Patients received a dose of 24 mg/d (given as 12 mg twice daily; mean dose = 21.6 mg) that could be reduced to 12 mg/d (given once daily at bedtime) any time after day 35 at the investigator's discretion.

A total of 72/173 patients (41.6%) completed the open-label extension. Treatment-emergent adverse events (TEAEs), most mild to moderate in severity, included headache (13.9%), weight increase (9.2%), dizziness (6.9%), nausea (6.4%), sedation (6.4%), and insomnia (5.2%). The only notable dose-related TEAEs were increased weight and headache. Levels of serum glucose, lipids, and prolactin were essentially unchanged or decreased during treatment. In general, akathisia and extrapyramidal symptoms (EPS) improved or were unchanged during treatment. There was no signal of worsening of efficacy based on changes from baseline in the Positive and Negative Syndrome Scale-Total.

This study further supports the long-term safety and tolerability of iloperidone for the treatment of schizophrenia, including iloperidone's favorable effect on metabolic laboratory parameters and low propensity to cause akathisia or EPS.

Family caregivers of cancer patients suffer from physical, psychological, and social distress and therefore are often referred to as second order patients. Akathisia is a common side effect of antipsychotics and antidepressants that causes great discomfort and even agitation and is often described by patients administered these drugs as the most distressing side effect of their treatment. Several studies of akathisia as a cause of distress in cancer patients have been reported. However, akathisia has not been reported as a cause of distress in family caregivers of cancer patients.

A 74-year-old spouse caregiver who was under treatment for major depressive disorder was not able to visit the hospital where her husband, a terminally ill cancer patient, was being treated. Initially, the spouse caregiver thought that she could not visit the hospital because of the symptoms of her depression and her grief about losing her husband. However, careful clinical examination revealed that she was suffering from akathisia in addition to her grief.

Discontinuation of her sulpiride treatment resulted in the disappearance of her akathisia symptoms, and therefore she became able to visit the hospital and care for her terminally ill husband.

Drug induced akathisia is a cause of distress in spouse caregivers taking certain drugs. It is important for clinicians to realize that family caregivers might suffer from not only socioeconomic, physical, and psychological problems but also side effects of medication.

Akathisia is a common adverse effect of antipsychotics and, less commonly, antidepressants. Akathisia can cause great discomfort and is often described by the patient as a most distressing sensation; however, the condition is often underdiagnosed or misdiagnosed. In oncological settings, neuroleptics and antidepressants that induce akathisia are also administered. However, reports of akathisia in oncology settings are few and a case of akathisia in a bedridden patient has not been reported as far as we know.

A 72-year-old man with esophageal cancer who could not sit down or stand up was administered 5 mg/day haloperidol to relieve agitation as a symptom of major depressive disorder. Three days after the administration of haloperidol, the agitation had become worse. Careful observation revealed that the patient sometimes showed slight rubbing movement of the lower extremities and slight twisting movements of the body, which were not observed before the administration of haloperidol. The patient moved his body and lower extremities to relieve restlessness, which had developed after the administration of haloperidol. Although symptoms were atypical, akathisia was suspected and discontinuation of haloperidol resolved the symptoms.

In patients with poor performance status, clues leading to the correct diagnosis of akathisia might be absent, which would not be the case in patients who were able to walk, stand up, or sit down. Careful observations of patients before and after the administration of drugs that may cause akathisia may be required to ensure correct diagnosis.

There is substantial evidence that tricyclic antidepressants are effective in the management of chronic pain, including cancer pain. In oncological settings, these agents are used as adjuvant analgesic drugs. However, cases of akathisia due to tricyclic antidepressants used as adjuvant analgesic therapy have not previously been reported.

Two cancer patients experiencing chronic pain who were refractory to nonsteroidal anti-inflammatory drugs and opioids were prescribed amoxapine as an adjuvant analgesic therapy for neuropathic pain. These patients developed inner restlessness and restless physical movements after amoxapine was prescribed. Although symptoms were atypical, akathisia was suspected and discontinuation of amoxapine resolved the symptoms.

Akathisia should be considered in patients receiving adjuvant analgesic therapy with tricyclic antidepressants. Early detection and appropriate treatment will relieve this distressing symptom. Restless movements involving parts of the body other than the legs may be the clue to the diagnosis.

Complications of neuropsychiatric disorders are often detected in cancer patients. Adjustment disorders, depression, or delirium are common psychiatric disorders in these patients, and drug-induced neuropsychiatric problems are sometimes referred for psychiatric consultation. Prochlorperazine and other antiemetic drugs that are phenothiazine derivates are also reported to cause akathisia due to the blockade of the dopamine receptor in the central nervous system, but the prevalence of akathisia in patients undergoing cancer treatment has not been reported. This study seeks to explore the prevalence of such drug-induced syndromes (e.g., akathisia) in this population.

This present study was a prospective study. The subjects of this study were 483 consecutive patients with cancer who had been referred to the Department of Psychiatry in Kanagawa Prefecture Cancer Center from February 1, 2004, to November 30, 2005. Trained psychiatrists conducted a nonstructured psychiatric interview and neurologic examination to establish psychiatric diagnoses according to DSM-IV and the presence or absence of drug-induced extra pyramidal symptoms. The past and current medications used in their cancer treatment were also examined in detail for an accurate evaluation.

A psychiatric diagnosis was made in 420 (87.0%) of the 483 cancer patients examined, and akathisia, a drug-induced movement disorder, was unexpectedly prevalent among the patients; 20 of 420 (4.8%) patients had developed akathisia from an antiemetic drug, prochlorperazine.

Diagnosing such adverse drug reactions may be difficult due to complicating factors in cancer treatment, and the inner restlessness observed in akathisia is likely to be regarded as a symptom of a primary psychiatric disorder. The authors suggest that oncologists should optimize the use of antiemetic drugs and be aware of akathisia as a possible complication of cancer treatment.